Cross-talk between CXC chemokine ligand 10-CXC chemokine receptor 3 axis and CC chemokine ligand 17-CC chemokine receptor 4 axis in the pathogenesis of oral lichen planus / 华西口腔医学杂志

OBJECTIVES@#This study aimed to determine whether a correlation existed between CXC chemokine ligand 10 (CXCL10)-CXC chemokine receptor 3 (CXCR3) and CC chemokine ligand 17 (CCL17)-CC chemokine receptor 4 (CCR4) in the pathogenesis of oral lichen planus (OLP).@*METHODS@#Peripheral blood of OLP patients (non-erosive and erosive groups) and healthy controls were collected, and T cells were isolated and purified. T cells were co-cultured with three groups: blank, anti-CXCR3, and anti-CCR4. CXCR3 and CCR4 expression were detected by flow cytometry, and CXCL10 and CCL17 were detected by enzyme-linked immunosorbent assay, respectively.@*RESULTS@#The purities of T cells were all >95% in the three groups (@*CONCLUSIONS@#Two axes interact with each other in the pathogenesis of OLP and may play different roles in its occurrence and development.

Expression and Clinical Significance of CXCR3 in Mantle Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression and clinical significance of chemokine receptor CXCR3 in mantle cell lymphoma (MCL).@*METHODS@#Flow cytometry was used to detect CXCR3 in lymph nodes and extranodal tissues in 25 newly diagnosed MCL patients. The correlation of the expression of CXCR3 level with clinical features and prognostic factors was analyzed.@*RESULTS@#Twenty-five tumor submitted specimens all expressed CXCR3 at varied degrees. The expression levels of CXCR3 in lymph nodes (LN) and bone marrow (BM) were higher than those in peripheral blood (PB), and the expression intensity in BM positively correlated with the involved tumor numbers. The absolute values of lymphocytes and hemoglobins level in PB of CXCR3high group were significantly lower than those in CXCR3low group (all P0.05). The overall response rate (ORR) in CXCR3low group was significantly higher than that in CXCR3high group (P=0.001). The expression level of CXCR3 in MCL cells of the effective group was significantly lower than that before treatment (P=0.038), and the CXCR3 expression in the ineffective group was significantly higher than that before treatment (P=0.002). After following up, it was found that the 3-year overall survival (OS) time and progression-free survival (PFS) time in CXCR3high group were significantly shorter than those in CXCR3low group (all P<0.05).@*CONCLUSION@#The expression level of CXCR3 in MCL closely relates with early metastasis and prognosis. CXCR3 can be used as one of the indicators for clinical efficacy and prognosis evaluation.

Expression and clinical significance of chemokine CXCL10 and its receptor CXCR3 in hepatocellular carcinoma / 北京大学学报(医学版)

OBJECTIVE@#To explore the expression and clinical significance of chemokine CXCL10 and CXCR3 in hepatocellular carcinoma (HCC).@*METHODS@#The expression and prognostic of CXCL10 and CXCR3 in HCC tumor tissues and non-tumor tissues were analyzed in two different publicly available databases the Cancer Genome Atlas (TCGA) and Liver Cancer Institute (LCI). In addition, quantitative real-time PCR (qPCR) was used to detect the mRNA expression of CXCL10 and CXCR3 in 45 HCC clinical samples with HBV infection background. Pearson correlation and Spearman rank correlation were used to determine the correlation between the expression level of CXCL10 and CXCR3 in tumor and non-tumor tissues.@*RESULTS@#In TCGA database, the expression of CXCL10 in HCC tumor tissues was significantly higher than that in non-tumor tissues (nonpaired samples: 3.379±2.081 vs. 2.213±2.274, P<0.001; paired samples: 3.159±2.267 vs. 2.213±2.274, P=0.018). Similarly in LCI datebase (7.625±1.683 vs. 7.287±1.328, P=0.009). And higher CXCL10 expression was significantly associated with a better prognosis in the patients with HCC both in TCGA and LCI database (P=0.107, P=0.002). In TCGA database, the expression of CXCR3 in HCC tumor tissues was significantly higher than that in non-tumor tissues (nonpaired samples: -0.906±1.697 vs. -1.978±1.629, P<0.001; paired samples: -1.329±1.732 vs. -1.978±1.629, P=0.037), while lower in LCI database (3.989±0.339 vs. 4.074±0.309, P=0.003). In both databases, higher CXCR3 expression was significantly associated with a better prognosis in the HCC patients (P=0.004, P=0.014). Furthermore, in TCGA database, the expression level of CXCL10 and CXCR3 was positively correlated both in HCC tumor tissues and matched non-tumor tissues (r=0.584, P<0.001; r=0.776, P<0.001). The qPCR assay showed that the expression of CXCL10 in HBV-related HCC tumor tissues was significantly higher than those in normal liver tissues [0.479(0.223, 1.094) vs. 0.131(0.106, 0.159), P=0.010], and the expression in HBV-related non-tumor tissues was also significantly higher than those in normal liver tissues [0.484(0.241, 0.846) vs. 0.131(0.106, 0.159), P<0.001]. The same was true as CXCR3 [0.011(0.006, 0.019) vs. 0.002(0.001, 0.004), P=0.004; 0.016(0.011, 0.021) vs. 0.002(0.001, 0.004), P<0.001]. However there was no significant difference of CXCL10 and CXCR3 between tumor tissues and matched non-tumor tissues (P=1.000, P=0.374).@*CONCLUSION@#Expression of CXCL10 was up-regulated in HCC tissues, expression of CXCR3 was down-regulated in HBV-related HCC tissues, and the higher expression of both genes was correlated with better overall survival in HCC patients.

Chemokine Receptor CXCR3 in the Spinal Cord Contributes to Chronic Itch in Mice / 神经科学通报·英文版

Recent studies have shown that the chemokine receptor CXCR3 and its ligand CXCL10 in the dorsal root ganglion mediate itch in experimental allergic contact dermatitis (ACD). CXCR3 in the spinal cord also contributes to the maintenance of neuropathic pain. However, whether spinal CXCR3 is involved in acute or chronic itch remains unclear. Here, we report that Cxcr3 mice showed normal scratching in acute itch models but reduced scratching in chronic itch models of dry skin and ACD. In contrast, both formalin-induced acute pain and complete Freund's adjuvant-induced chronic inflammatory pain were reduced in Cxcr3 mice. In addition, the expression of CXCR3 and CXCL10 was increased in the spinal cord in the dry skin model induced by acetone and diethyl ether followed by water (AEW). Intrathecal injection of a CXCR3 antagonist alleviated AEW-induced itch. Furthermore, touch-elicited itch (alloknesis) after compound 48/80 or AEW treatment was suppressed in Cxcr3 mice. Finally, AEW-induced astrocyte activation was inhibited in Cxcr3 mice. Taken together, these data suggest that spinal CXCR3 mediates chronic itch and alloknesis, and targeting CXCR3 may provide effective treatment for chronic pruritus.

Serosal Cavities Contain Two Populations of Innate-like integrin α4highCD4+ T Cells, Integrin α4β1+α6β1+α4β7− and α4β1+α6β1−α4β7+ Cells

We previously reported peritoneal innate-like integrin α4 (CD49d)highCD4+ T cells that provided help for B-1a cells. Here we analyzed the expression of various integrin chains on the peritoneal and pleural integrin α4highCD4+ T cells and investigated the functional heterogeneity of the subpopulations based on the integrin expression. Pleural cavity contained a lower ratio of integrin α4highCD4+ T cells to integrin α4lowCD4+ T cells than peritoneal cavity, but the pleural integrin α4highCD4+ T cells have the same characteristics of the peritoneal integrin α4highCD4+ T cells. Most of integrin α4highCD4+ T cells were integrin β1highβ7−, but a minor population of integrin α4highCD4+ T cells was integrin β1+β7+. Interestingly, the integrin α4highβ1highβ7− CD4+ T cells expressed high levels of integrin α4β1 and α6β1, whereas integrin α4highβ1+β7+ CD4+ T cells expressed high levels of integrin α4β1 and α4β7, suggesting an alternative expression of integrin α6β1 or α4β7 in combination with α4β1 in respective major and minor populations of integrin α4highCD4+ T cells. The minor population, integrin α4highβ1+β7+ CD4+ T cells, were different from the integrin α4highβ1highβ7− CD4+ T cells in that they secreted a smaller amount of Th1 cytokines upon stimulation and expressed lower levels of Th1-related chemokine receptors CCR5 and CXCR3 than the integrin α4highβ1 highβ7− CD4+ T cells. In summary, the innate-like integrin α4highCD4+ T cells could be divided into 2 populations, integrin α4β1+α6β1+α4β7− and α4β1+α6β1−α4β7+ cells. The functional significance of serosal integrin α4β7+ CD4+ T cells needed to be investigated especially in view of mucosal immunity.

Roles of CXCR3 on lymphocytes and IP-10 of peripheral blood in infants with bronchiolitis / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the roles of chemokine receptor 3 (CXCR3) on lymphocytes and interferon-γ-inducible protein-10 (IP-10) of peripheral blood in childhood bronchiolitis.</p><p><b>METHODS</b>Fifty-five children with bronchiolitis were classified into Group I (with allergic factors) and Group II (without allergic factors). Twenty-eight children with noninfectious diseases were enrolled randomly as the control group. The expression of CXCR3 (CD183 as its molecular marker) on lymphocytes of peripheral blood was detected by flow cytometry. Serum IP-10 level was measured using ELISA.</p><p><b>RESULTS</b>The expression of CD183(+) cells on CD4(+) and CD8(+) lymphocytes in peripheral blood in children with bronchiolitis from both Group I and Group II was significantly higher than that in the control group (P<0.05), and Group I had higher expression of CD183(+) cells on CD4(+) and CD8(+) lymphocytes than Group II (P<0.05).Serum IP-10 levels in Group I and Group II were significantly higher than those in the control group (P<0.05). However, there was no significant difference in serum IP-10 levels between Group I and Group II.</p><p><b>CONCLUSIONS</b>CXCR3 and IP-10 are involved in the pathogenesis of bronchiolitis, and CXCR3 is associated with allergic factors.</p>

IFN-stimulated genes upregulation pattern in Chronic Hepatitis C

Background: The development of effective tools for the large-scale analysis of gene expression has provided new insights into the involvement of gene networks and regular pathways in various disease processes. The chemokine receptor CXCR3 is a G protein-coupled receptor found predominantly on T cells that is activated by three ligands as follow: CXCL9 [Mig], CXCL10 [IP-10] and CXCL11 [I- TAC], and play a key role in immune and inflammatory responses by promoting recruitment and activation of different subpopulations of leukocytes. Aim of the work: The study is a logical functional approach for the development of serum markers chemokines that bind to CXC chemokine receptor 3 to determine whether they play a role in the future of immune system to clear HCV, these chemokines: CXCL9, CXCL10 and CXCL11

Patients and methods: 131 male and female patients with chronic hepatitis C virus [CHCV] infection, their age ranges between 22 and 55 years,selected from the National Hepatology and Tropical Medicine Research Institute. The included patients were divided to two groups, the first group: 80 patients were investigated for the predictive values of CXCL9,10,11 and CXCR3 chemokines in peripheral blood mononuclear cells [PBMCs], the second group were fifty one patients analyzed for the expression of surface markers on CD8+T cells. Twenty healthy individuals were included to serve as controls for each group. All the patients and controls were subjected to the following: history, clinical examination, abdominal ultrasonography and collection of blood samples for routine laboratory investigation and serological assay

Results: Chemokine CXCL9, CXCL10, CXCL11 and their receptor CXCR3 expression levels are induced in PBMCs during CHCV infection, associated with increased the expression levels of CD8+T cells in CHCV patients

Conclusion: The interaction between chemokines and their receptors is essential in recruiting HCV-specific T cells to control the infection

Recommendations: The regulation of chemokines and their receptors could be a future potential therapeutic target to decrease liver inflammation and to increase specific T cell migration to the infected liver, the blocking of chemokines and chemokine receptor engagement is a therapeutic strategy that should be explored in the near future for non-responders to current anti-HCV therapy

Pentoxifylline attenuates cigarette smoke-induced overexpression of CXCR3 and IP-10 in mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cigarette smoke-induced emphysema is associated with overexpression of the chemokine receptor CXCR3 and its ligands. Previously, we have demonstrated that pentoxifylline (PTX) alleviated cigarette smoke-induced emphysema. The aim of this study was to determine if the overexpression of CXCR3 and its ligand interferon-inducible protein-10 (IP-10) that was elicited by smoke exposure were attenuated by PTX.</p><p><b>METHODS</b>(1) The study in vitro: a given number of RAW264.7 macrophages with decreasing concentrations of PTX in the culture medium were challenged with cigarette smoke extract (CSE); (2) The study in vivo: male BALB/c mice were randomized into four groups, i.e., sham-smoke, smoke only, smoke with 2 mg/kg PTX, and smoke with 10 mg/kg PTX. The smoke exposure time was 90 minutes once a day, 6 days a week for 16 weeks. PTX was given intraperitoneally before each episode of smoke exposure. Interferon (IFN)-γ and IP-10 in broncho-alveolar lavage fluid (BALF) and in culture medium were measured by enzyme-linked immunosorbent assay (ELISA). IP-10 mRNA in lung tissue was assessed by RT-PCR. CXCR3 positive cells in lung sections were visualized by immunochemistry staining.</p><p><b>RESULTS</b>Up-regulation of IFN-γ and IP-10 in the culture medium of macrophages elicited by CSE was inhibited by PTX in a dose-dependent manner. Chronic cigarette smoke exposure led to overexpression of IFN-γ and IP-10 in BALF, upregulation of IP-10 mRNA and increased infiltration of CXCR3(+) cells into lung parenchyma. Administration of PTX decreased the level of IFN-γ from (6.26 ± 1.38) ng/ml to (4.43 ± 0.66) ng/ml by low dose PTX or to (1.74 ± 0.28) ng/ml by high dose PTX. IP-10 was reduced from (10.35 ± 1.49) ng/ml to (8.19 ± 0.79) ng/ml by low dose PTX or to (7.51 ± 0.60) ng/ml by high dose PTX. The expression of IP-10 mRNA was also down-regulated (P < 0.05). But only with a high dose of PTX was the ratio of CXCR3(+) cells decreased; 15.2 ± 7.3 vs. 10.4 ± 1.8 (P < 0.05).</p><p><b>CONCLUSION</b>PTX attenuates cigarette smoke-induced overexpression of chemokine receptor CXCR3 and its ligand IP-10, which is relevant to its inhibitory effect on pulmonary emphysema.</p>

Expression of CXCR3 and CCR5 chemokine receptor in spleens of patients with primary immune thrombocytopenia / 中华血液学杂志

<p><b>OBJECTIVE</b>To study CXCR3 and CCR5 chemokine receptor expression in spleens of patients with primary immune thrombocytopenia (ITP) and its clinical significance.</p><p><b>METHODS</b>The splenectomy specimens from 10 ITP patients (ITP group) and 8 patients with traumatic splenic rupture (normal control group) were studied. Immunohistochemistry (IHC) was used to study the positive rate of CXCR3 and CCR5. Western blot was performed to detect CXCR3 and CCR5 protein expression, while real-time polymerase chain reaction (RT-PCR) was conducted to analyze their mRNA expression.</p><p><b>RESULTS</b>The positive rate of CXCR3 and CCR5 were both higher in ITP group (90% and 100%, respectively) than those in control group (75% and 87.5%, respectively)(P < 0.05). The differences were statistically significant (P < 0.05). Protein and mRNA level of CXCR3 in ITP group were 3.0 and 3.5 times as high as those in control group, respectively. Those of CCR5 in ITP group were 1.2 and 1.7 times as high as those in control group, respectively.</p><p><b>CONCLUSION</b>High expression of CXCR3 and CCR5 may play a part in the splenic immune disorders in patients with ITP.</p>

Significance of chemokine receptor CXCR3 expression in breast cancer / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the expression of CXCR3 and its association with clinicopathologic features in breast carcinoma.</p><p><b>METHODS</b>The expression level of CXCR3 in 18 samples of breast cancer and corresponding normal tissues was investigated using reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time RT-PCR analysis. Immunohistochemistry was carried out to examine the expression of CXCR3 in 80 breast cancers, 20 fibroadenomas and 15 normal breast tissues.</p><p><b>RESULTS</b>(1) RT-PCR and real-time RT-PCR analysis showed a higher level of CXCR3 in breast cancer tissues than that in the corresponding normal breast tissues (P < 0.05). (2) Immunohistochemistry analysis showed that the positive rate of CXCR3 in breast cancer tissues was significantly higher than that in fibroadenomas and the normal breast tissues (P < 0.05). The expression level of CXCR3 in the lymph node-positive group was higher than that in the lymph node-negative group (P < 0.05). The expression of CXCR3 was positively correlated with the number of lymph nodes involved by metastasis, tumor size and pTNM tumor stage (P < 0.05).</p><p><b>CONCLUSIONS</b>Chemokine receptor CXCR3 was up-regulated in breast cancer, and was associated with the progression of breast cancer. CXCR3 might be a novel molecular marker to predict lymph node metastasis and prognosis of breast cancer.</p>

Cytotoxicity of dichloroacetic acid in lymphocyte and expression of chemokine receptor CXCR2 and chemokine receptor CXCR3 mRNA / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore the effects of trichloroethylene (TCE) and its by-products (trichloroacetic acid, TCA; dichloroacetic acid, DCA) on the normal human peripheral blood lymphocyte and the role of DCA in dermatitis medicamentosa- like induced by trichloroethylene (DMLT).</p><p><b>METHODS</b>Lymphocyte was isolated from peripheral venous blood, and cytotoxicity of human lymphocytes treated with different concentrations (0.02 approximately 30.00 mmol/L) of DCA was determined at indicated times (2 h and 4 h) based on the MTS assay. Action of DCA on cell viability, membrane integrity was assessed by neutral red uptake (NRU) assay and lactate dehydrogenase (LDH) release test and measurement of superoxide dismutase (SOD) activity. Fluorescence quantitative reverse transcription polymerase chain reaction (FQ-RT-PCR) was employed for detection and quantization of the chemokine receptor CXCR2 and chemokine receptor CXCR3 mRNA in peripheral blood lymphocyte treated with different concentrations of DCA.</p><p><b>RESULTS</b>DCA had a more vital effect on peripheral blood lymphocyte than TCE and TCA. A concentration-dependent release of LDH was observed at 4 h after cells were exposed to different doses of DCA (0.88, 1.75, 3.50 and 7.00 mmol/L) (P < 0.05), and DCA also caused an inhibition of SOD activity in a concentration-dependent manner (P < 0.05). The results of FQ- RT- PCR indicated that CXCR2 and CXCR3 mRNA were all over- expression. At 48 h after the DCA of 0.5 mmol/L and 10.00 mmol/L was used, CXCR2 and CXCR3 mRNA were 10.34, 5.66-fold and 19.43, 8.75-fold of those in the control group (P < 0.01).</p><p><b>CONCLUSION</b>DCA is of a great cytotoxicity and may be one of crucial evocators on DMLT.</p>

Relationship between expression of chemokine receptors CCR3, CCR5 and CXCR3 on CD4(+) T cells and spontaneous abortion in mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Previous studies have shown that local immune cells in the feto-maternal interface are recruited from peripheral blood, and that chemokines and their receptors play an initial and key role in this recruitment process. In this study, we aimed to determine whether spontaneous abortion is associated with the expression of chemokine receptors CCR3, CCR5, and CXCR3 on CD4(+) T cells.</p><p><b>METHODS</b>Peripheral blood, spleen, and thymus were collected from the spontaneous abortion mouse model CBA/JxDBA/2 (SA group, n = 14), the normal pregnant mouse model CBA/JxBALB/c (NP group, n = 13), and normal non-pregnant CBA/J mice (NNP group, n = 11). The number of chemokine receptors CCR3, CCR5, and CXCR3 expressed on CD4(+) T cells was measured by double-label flow cytometry (FCM) method.</p><p><b>RESULTS</b>In peripheral blood, the SA group had significantly lower CCR3 expression (P < 0.01) and higher CCR5 and CXCR3 expression (P < 0.01) on CD4(+) T cells than did the NP group. But comparing these chemokines between the SA and NNP groups, there was no significant difference (P > 0.05). In spleen, the SA group expressed significantly lower CCR3 expression (P < 0.01) and higher CCR5 and CXCR3 expression (P < 0.05) on CD4(+) T cells than did the NP group. When compared with the NNP group, the SA group had significantly higher CCR3 expression (P < 0.01), but was not statistically different with regards to the other two chemokines (P > 0.05). In thymus, the SA group had significantly lower CCR3 expression (P < 0.05) and higher CXCR3 expression (P < 0.05) on CD4(+) T cells than the NP group, with no significant difference in CCR5 expression (P > 0.05). Compared with the NNP group, the SA group had higher CCR3 expression (P < 0.01), but there was no statistical difference in CXCR3 and CCR5 expression (P > 0.05) between the two groups.</p><p><b>CONCLUSION</b>The abnormal expression of CCR3, CCR5 and CXCR3 on CD4(+) T cells may play an important role in the pathogenesis of spontaneous abortion.</p>

Expression of chemokine receptors CCR3, CCR5 and CXCR3 on CD4(+) T cells in CBA/JxDBA/2 mouse model, selectively induced by IL-4 and IL-10, regulates the embryo resorption rate / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Chemokines and their receptors have been a research focus in transplantation immunology. Chemokines and their receptors play a role in lymphocyte recruitment and differentiation process. This study aimed to observe whether IL-4 and IL-10 may regulate the expression of chemokine receptors CCR3, CCR5 and CXCR3 on CD4(+) T cells in CBA/JxDBA/2 mouse model and to explore the role of CCR3, CCR5, CXCR3 in immune tolerance in pregnancy.</p><p><b>METHODS</b>The mouse model of spontaneous abortion (CBA/JxDBA/2) and the normal pregnant mouse model (CBA/JxBALB/c) were used. CBA/JxDBA/2 mice were injected with IL-4 (CBA/JxDBA/2-IL-4), IL-4 and IL-10 (CBA/JxDBA/2-IL-4+IL-10), or normal saline (CBA/JxDBA/2-NS) as a control. The expression of CCR3, CCR5 and CXCR3 on CD4(+) T cells from mouse peripheral blood was measured by the double-labelled FCM method, and the embryo resorption rate was also examined.</p><p><b>RESULTS</b>The embryo resorption rate in the CBA/JxDBA/2 group without any treatment was significantly higher than that in the CBA/JxBALB/c group (17.9% vs 3.7%, P < 0.01). The embryo resorption rate in the CBA/JxDBA/2 group immunized with IL-4 or IL-4 together with IL-10 was significantly decreased, compared with that in the control and NS groups respectively. CCR3 expression on CD4(+) T cells in the CBA/JxDBA/2 group without any treatment was significantly lower than that in the CBA/JxBALB/c group (0.3738 +/- 0.3575 vs 1.2190 +/- 0.2772, P < 0.01); both CCR5 (3.0900 +/- 1.5603 vs 1.2390 +/- 0.6361, P < 0.01) and CXCR3 (2.4715 +/- 0.9074 vs 0.9200 +/- 0.5585, P < 0.01) expressions on CD4(+) T cells of the CBA/JxDBA/2 group without any treatment were significantly higher than those of the CBA/JxBALB/c group. Significant up-regulation of CCR3 and down-regulation of CXCR3 were found in the CBA/JxDBA/2 group treated with IL-4 (CCR3: 2.0360 +/- 0.6944, CXCR3: 1.3510 +/- 0.5263, P < 0.01) or IL-4 and IL-10 (CCR3: 1.8160 +/- 1.0947, CXCR3:1.0940 +/- 0.7168, P < 0.01). Because of the CCR5, IL-4 and IL-10 (1.9400 +/- 0.8504 vs 3.0900 +/- 1.5603, P < 0.05), but IL-4 alone (2.5310 +/- 1.3595 vs 3.0900 +/- 1.5603, P > 0.05) treatment significantly decreased the expression of CCR5 in CBA/JxDBA/2.</p><p><b>CONCLUSIONS</b>The abnormal expression of CCR3, CCR5 and CXCR3 on CD4(+) T cells may play an important role in the pathogenesis of spontaneous abortion. The pregnancy immune tolerance may be induced through selective induction of CCR3, CCR5 and CXCR3 expressions by IL-4 together with IL-10.</p>

Selective addition of CXCR3+CCR4-CD4+ Th1 cells enhances generation of cytotoxic T cells by dendritic cells in vitro

Increasing importance is being given to the stimulation of Th1 response in cancer immunotherapy because its presence can shift the direction of adaptive immune responses toward protective immunity. Based on chemokine receptor expression, CXCR3+CCR4-CD4+ T cells as Th1-type cells were investigated its capacity in monocyte-derived dendritic cell (DC) maturation and polarization, and induction of antigen specific cytotoxic T lymphocytes (CTL) in vitro. The levels of IL-4, IL-5 and IL-10 were decreased to the basal level compared with high production of IFN-gamma, TNF-alpha, and IL-2 in CXCR3+CCR4-CD4+ T cells stimulated with anti-CD3 and anti-CD28 antibodies. Co-incubation of activated CD4+ or CXCR3+CCR4-CD4+ T cells with DC (CD4+/DC or CXCR3+CD4+/DC, respectively) particularly up-regulated IL-12 and CD80 expression compared with DC matured with TNF-alpha and LPS (mDC). Although there was no significant difference between the effects of the CXCR3+CCR4-CD4+ and CD4+ T cells on DC phenotype expression, CXCR3+CD4+/DC in CTL culture were able to expand number of CD8+ T cells and increased frequencies of IFN-gamma secreting cells and overall cytolytic activity against tumor antigen WT-1. These results demonstrated that the selective addition of CXCR3+CCR4-CD4+ T cells to CTL cultures could enhance the induction of CTLs by DC in vitro, and implicated on a novel strategy for adoptive T cell therapy.

Expression of CD38 and CXCR3 in children with atopic dermatitis

Atopic dermatitis [AD] is a chronic or chronically relapsing inflammatory skin disease with a prevalence ranging from 10% to 20% in children of developed countries. Skin-infiltrating leukocytes play a pivotal role in the initiation and amplification of atopic skin inflammation. The cytokines produced by T helper-,2 [Th2] cells are crucial factors in the induction and maintenance of the disease. to study the percentage of expression and mean fluorescence intensity[ MFI] of the activation marker CD38 and the chemokine receptor CXCR3 on peripheral blood CD3+ lymphocytes in children with atopic dermatitis. Also total serum IgE and absolute differential count were evaluated .This might be targets for therapy in disease. This study was conducted on thirty cases of AD children. Their age range was 3- 10 years. Also non atopic fifteen children age and sex matched with disease group were included as a control group. The percentage of expression of the CD38, CXCR3 and MFI were analyzed by flow- cytometry on peripheral blood CD3+ T lymphocytes. Also total serum IgE levels was measured by immunonephelometry. The absolute eosinophil, absolute lymphocytes, absolute neutrophil count were evaluated. The mean percentage of CD38 expression on CD3 + lymphocytes and MFI were 70.5% and 5.8 respectively in AD children compared with 17.8% and 5.1 in non -atopic children healthy control [p < 0.01 and p > 0.05 respectively]. The mean percentage of CXCR3 expression on CD3+ T lymphocytes and MFI in AD children were 17.9% and 2.9 respectively compared with 67.93%and 3.3 in healthy controls [p < 0.01 and p > 0.05 respectively]. The mean of the total serum IgE in the patient group was 199.3 lU/ml compared with 62.27 lU/ml in-non-atopic children [p < 0.01]. These results suggest that there is a relation between atopic conditions and an increase in peripheral blood T lymphocyte expressing CD38% and decrease expression of CXCR3%.The presence of high expression of CD38 in atopic patients seems to confirm the role of this molecule as an activation marker useful for evaluation of Th2 immune response. whereas CXCR3-expression on CD3+ lymphocytes decreased in AD than normal control as the chemokine receptor profile determine the migratory patterns of leukocytes. These results may suggest the dysbalance between Th1/ Th2 in AD patients

CXCR3 and CXCR4 receptors expression on peripheral blood T-lymphocytes from patients with rheumatoid arthritis

Rheumatoid arthritis [RA] is a chronic inflammatory condition that affects multiple joints. Chemokines and their receptors are involved together in the development and perpetuation of inflammation Chemokine receptors CXCR3 and CXCR4 are among the main regulators of T cell recruitment in autoimmune diseases. The present study aimed at detection of the frequency of CXCR3 and CXCR4 chemokine receptors expression on peripheral blood T-lymphocytes in patients with rheumatoid arthritis in an attempt to identify suitable targets for therapeutic intervention. Twenty eight patients with rheumatoid arthritis, selected from those attending the Rheumatology and Rehabilitation outpatient clinic, Ain Shams University Hospitals, were studied. Ten age and sex matched healthy subjects were served as controls. All patients were subjected to full medical history, thorough clinical examination, evaluation of the disease activity using disease activity score 28 [DAS28] and radiological assessment by plain X rays of both hands and feet [posterior - antero views] for the erosive changes. Peripheral blood lymphocytes analysis was performed by flow cytometry using anti-CD3, anti-CXCR3 and anti-CXCR4 monoclonal antibodies. High statistically significant difference was determined between patients and controls as regard relative count of T- lymphocytes expressing CXCR4 receptors [35.068 +/- 5.098, 23.59 +/- 4.601, respectively and P< 0.001]. Also, there was a significant positive correlation between relative count of T- lymphocytes expressing CXCR4 receptors and disease activity using disease activity sore 28 [DAS28] disease duration and the hemoglobin level. On the other hand, no significant correlation was determined between relative count of T- lymphocytes expressing CXCR3 receptors and any of the clinical and laboratory parameters of patients. Increased expression of CXCR4 on peripheral T cells of Patients [RA Patients] and its positive correlation with the disease activity indicate that this chemokine receptor plays a central role in the process of chronic inflammation in RA and suggests that targeting CXCR4 could provide a new treatment for this disease. Although our data did not prove that CXCR3 expression is higher in patients with RA, however, it can be expected that it is involved in the inflammatory process based on reported functional studies

Effects of mouse bone marrow mesenchymal stem cells on the expression of chemokine receptors of spleenocytes after phytohemagglutinin stimulation / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To explore the effect of mouse bone marrow mesenchymal stem cells (MSCs) on the expression of chemokine receptors in T lymphocytes in vitro.</p><p><b>METHODS</b>Mouse bone marrow MSCs were separated with Percoll, cultured and expanded in low glucose DMEM. C57BL/6 mouse spleenocytes were cultured in the 24-hole flasks by the density of 1 x10(6)/hole. Phytohemagglutinin (PHA) was then added to the holes and cultured for 72 hrs. This study consisted of three groups. Groups A and B were co-cultured by adding MSCs as the ratio of 0.1 and 0.01 to spleenocytes respectively. The control group was cultured without MSCs. Three days later the suspended spleenocytes were harvested for detecting the expression of three chemokine receptors CXCR3, CCR5 and CCR7 in T lymphocytes by the flow cytometry.</p><p><b>RESULTS</b>The expression of CD3(+)CCR5(+) and CD3(+)CCR7(+) were statistically different among the three groups. Group A had the strongest expression, followed by group B and the control group. The expression of CD3(+)CXCR3(+) in group A was statistically higher than that in group B and the control group.</p><p><b>CONCLUSIONS</b>MSCs could up-regulate the expression of chemokine receptors CXCR3, CCR5 and CCR7 in T lymphocytes stimulated by PHA.</p>

An expression plasmid encoding recombinant immunotoxin IP10-DT390 suppresses the experimental autoimmune encephalomyelitis / 生物医学工程学杂志

Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease of the central nervous system (CNS); it serves as a model for the human multiple sclerosis (MS). In mice, EAE is mediated by T cells specific for various myelin basic proteins which migrate from the periphery to the CNS. In search of a way to prevent the induction and progression of EAE, we observed the effects of recombinant immunotoxin IP10-DT390 on blocking or eliminating the active T cells in the EAE model. In this paper is presented an experimental gene therapy-based model in which the mice were made resistant to EAE induction by plasmid DNA encoding recombinant immunotoxin that was injected into the leg muscles of mice. The new immuno-biological construct could selectively impair autoreactive T-cell homing while the duration of clinical signs is shorter, and the new construct would not affect other components of the immune response. These data demonstrated the effectiveness of the constructs in the treatment of EAE and suggested its usefulness in the treatment of other autoimmune diseases.

Effects of blocking the CXC chemokine receptor 3 pathway on acute rejection of islet allograft / 中华外科杂志

<p><b>OBJECTIVE</b>To identify the effect of PNA CXCR3 on acute rejection of islet allograft.</p><p><b>METHODS</b>The mice islet transplant models were used. The mice were divided into three groups including saline group, PNA CXCR3 group and mismatch PNA group. In vitro the proliferation capability of T cell was assessed by proliferative responses. RT-PCR and western blot were used to detect the expression of mRNA and protein. Flow cytometry was applied to determine the expression level of CXCR3 in spleen CD3(+) T cells.</p><p><b>RESULTS</b>Compared with saline [(6.72 +/- 1.48) d] and PNA mismatch-treated recipients [(6.54 +/- 0.86) d], PNA CXCR3-treated recipients demonstrated statistically significant prolongation [(9.70 +/- 1.57) d] in functional allograft survival. The CXCR3 mRNA expression level of PNA CXCR3 group (1.06 +/- 0.07) was significantly down-regulated compared with saline (1.98 +/- 0.22) and PNA mismatch (1.87 +/- 0.10) group at the 7th day after transplant. The date showed that CXCR3 protein and lymphocytes proliferation capability was significantly down-regulated in PNA CXCR3 group compared with saline and PNA mismatch group (P<0.01).</p><p><b>CONCLUSIONS</b>The present study indicates that PNA CXCR3 can inhibit T cell activating and prolonging the survival time of islet allograft and has a substantial therapeutic effect on inhibiting acute allograft rejection.</p>

Expression of chemokine receptor CXCR3 mRNA in patients with atopic dermatitis / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the role of chemokine receptor CXCR3 in patients with atopic dermatitis.</p><p><b>METHODS</b>The expression of CXCR3 mRNA was measured by fluorescent quantitative polymerase chain reaction, and the relationship between CXCR3 mRNA expression and the disease severity (graded according to SCORAD index system) was assessed by correlation analysis.</p><p><b>RESULTS</b>CXCR3 mRNA expression was significantly higher in patients with atopic dermatitis than in healthy control subjects (P7lt;0.01), and showed obvious positive correlation with SCORAD index system.</p><p><b>CONCLUSION</b>These data suggest an important role of CXCR3 in the development and progression of atopic dermatitis.</p>