The CXCL9/10/11-CXCR3 axis as a predictor of COVID-19 progression: a prospective, case-control study

ABSTRACT Background: This study examined the relationship between levels of the chemokines CXCL9, CXCL10, CXCL11, and CXCR3 and mortality in patients with COVID-19.. Methods: A total of 71 patients hospitalized with COVID-19 and 35 health workers with no symptoms and negative SARS-CoV-2 PCR results were included in the study. CXCL9, CXCL10, CXCL11, and CXCR3 levels were measured in blood samples using enzyme-linked immunosorbent assays. Participants were divided into three groups: healthy individuals, patients with mild to moderate pneumonia, and patients with severe pneumonia. Patients were also divided into sub-groups according to the outcome: dead and survived. Results: Serum CXCL9, CXCL10, CXCL11, and CXCR3 levels were significantly higher in patients with severe COVID-19 than in those with non-severe COVID-19; were higher in both patient groups than in the control group; and were higher in patients who died than in those who survived. Lymphocyte counts, and fibrinogen and PaO2/FiO2 levels were significantly lower in patients with severe COVID-19 than in those with moderate disease. Patients with COVID-19 also had elevated neutrophil/lymphocyte ratios, neutrophil counts, and lactate dehydrogenase, C-reactive protein, D-dimer, and ferritin levels. Conclusions: This study confirmed that CXCL9, CXCL10, CXCL11, and CXCR3 levels are associated with disease severity in patients with COVID-19. These laboratory parameters can help to estimate disease severity and predict outcomes, and are useful in clinical decision-making.

CXCL10/CXCR3 Signaling in the DRG Exacerbates Neuropathic Pain in Mice / 神经科学通报·英文版

Chemokines and receptors have been implicated in the pathogenesis of chronic pain. Here, we report that spinal nerve ligation (SNL) increased CXCR3 expression in dorsal root ganglion (DRG) neurons, and intra-DRG injection of Cxcr3 shRNA attenuated the SNL-induced mechanical allodynia and heat hyperalgesia. SNL also increased the mRNA levels of CXCL9, CXCL10, and CXCL11, whereas only CXCL10 increased the number of action potentials (APs) in DRG neurons. Furthermore, in Cxcr3

Research progress on CXCR3 variants and their ligands in tumor microenvironment / 中国肿瘤生物治疗杂志

@#[摘 要] 恶性肿瘤是严重威胁人类生命的疾病之一，近年来免疫治疗已经成为肿瘤治疗的焦点，解决免疫治疗只对部分患者有效的问题迫在眉睫。在肿瘤微环境（tumor microenvironment，TME）中趋化因子介导细胞的定向移动，同时具有多种调节功能，既可以作用于免疫细胞，也可直接作用于肿瘤细胞，发挥了复杂的生物学作用。CXC趋化因子受体3（CXC chemokine receptor 3，CXCR3）通过与其同源CXC趋化因子配体9（CXC chemokine ligand 9，CXCL9）/10/11结合，不仅参与了肿瘤发生、侵袭并促进肿瘤相关血管的形成，同时也介导了免疫细胞向肿瘤组织中浸润，为无免疫反应性或免疫反应性差的“冷肿瘤”转变为免疫反应性的“热肿瘤”提供了新的思路，并且可能成为治疗的新靶点。这种抗肿瘤和促肿瘤的双重作用，似乎与CXCR3变体（CXCR3-A、CXCR3-B）发挥相反的作用密切相关。本文就近年来CXCR3变体CXCR3-A、CXCR3-B及其配体CXCL9/10/11在TME中作用的研究进展展开综述。

GLGZD improves cerebral ischemia-reperfusion injury in rats by inhibiting microglial activation / 中国药理学通报

Aim To study whether GLGZD exerts brain protection by affecting the activation of cortical microglia in cerebral ischemia-reperfusion rats. Methods The nylon thread plug was used to establish the MCAO model. After GLGZD treatment for seven days, mNSS was used to evaluate the neurological function of each group of rats, MRI to detect cerebral infarction volume in rats, TUNEL to detect the apoptotic rate of nerve cells, immunohistochemistry to detect TNF-α protein expression in ischemic cortical brain tissues, and RT-qPCR to detect mRNA expression of neuron-microglia interaction-related factors TWEAK, Fnl4, NIK, Rel B, CCL21, CXCR3 and microglial activation marker IBA-1 in ischemic cortical brain tissues. Results GL-GZD could significantly improve the neurological function of MCAO rats, and markedly reduce the infarct volume and apoptosis of ischemic cortical neurons in MCAO rats. It also could significantly down-regulate the expressions of TNF-a protein and TWEAK, Fnl4, NIK, Rel B, CCL21, CXCR3 and IBA-1 mRNA in ischemic cortex of MCAO rats. Conclusions GLGZD can significantly improve cerebral ischemia-reperfusion injury in rats, which may be related to inhibition of microglial cell activation by affecting TWEAK/Fn14/ CCL21/CXCR3 signaling pathway.

O receptor de quimiocina CXCR3/CD183 na tuberculose / The chemokine receptor CXCR3/CD183 in tuberculosis

Introdução: o receptor CXCR3/CD183 juntamente com seu indutor IFNy e seus ligantes CXCL9, CXCL10 e CXCL11 têm sido descritos como de grande importância na resposta imune do perfil T helper 1 (Th1). Este grupo de quimiocinas é expresso no microambiente e permite a migração de células ao sítio da infecção para combater o patógeno. Objetivo: revisar o atual estado da arte sobre o papel do receptor CXCR3/CD183 na tuberculose. Metodologia: o presente estudo inclui a revisão narrativa de 12 artigos que foram selecionados a partir de 74 artigos encontrados nas bases de dados PubMed e Sciencedirect entre primeiro de agosto e 31 de outubro de 2014. Resultados: diferentes abordagens vêm sendo utilizadas para o estudo desse receptor. A utilização de modelos animais como camundongos, coelhos e macacos é a mais comum. Porém, ensaios in vitro com células humanas do sangue periférico e efusão pleural também já foram utilizados para representar, com maior fidelidade, a resposta ao Mycobacterium tuberculosis (Mtb) pelo sistema imune humano. Esses estudos resultaram em importantes achados sobre o papel do receptor CXCR3 na tuberculose (TB), principalmente quanto à expressão em linfócitos e neutrófilos, assim como o padrão de coexpressão de outros receptores. Conclusão: o CXCR3 é o receptor de uma importante citocina (IP-10) induzida pelo IFN-gama, produzida na resposta Th1, eficaz na resposta à tuberculose. Nesse trabalho, resssalta-se que foram encontrados poucos estudos sobre o tema e isso demonstra a necessidade de realização de novas pesquisas, a fim de melhor investigar o papel desse importante receptor na tuberculose.

Introduction: the CXCR3/CD183 receptor along with its IFNy inducer and its ligands: the chemokines named CXCL9, CXCL10 and CXCL11 are of great importance in the Th1 (T helper 1) immune response. This group of chemokine modulates the migration of cells to the site of infection to defend against the pathogen. Objective: to investigate the current state of the art on the role of the receptor CXCR3/CD183 in tuberculosis. Methodology: the present study includes the narrative review of 12 articles that were selected from 74 articles found in the PubMed and Sciencedirect databases between August 1 and October 31, 2014. Results: different approaches have been used for the study of this receptor. The use of animal models such as mice, rabbits and monkeys is more common. However, in vitro assays with human peripheral blood cells and pleural effusion were also used to represent more faithfully the response to Mycobacterium tuberculosis (Mtb) by the human immune system. These studies resulted in significant findings on the role of the CXCR3 receptor in tuberculosis (TB), especially for expression in lymphocytes and neutrophils, as well as the pattern of co-expression of other receptors. Conclusion: CXCR3 is the receptor for an important cytokine (IP-10) induced by IFN-gamma, produced in the Th1 response, effective in responding to tuberculosis. In this work, it is emphasized that cheeses found few studies on the subject and demonstration, the need for conducting research, in order to better investigate the role of this important receptor in tuberculosis.

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.

Expression of CXCL10 ,CXCR3 and T cell subsets in peripheral blood and effect of compound Chinese medicine on it in patients with advanced vitiligo / 重庆医学

Objective To detect the expression levels of peripheral blood CXCL10 and its receptor CXCR3 and T cell subsets in of the patients with advanced vitiligo and the influence of compound Chinese medicine on it.Methods Flow cytometry was used to detect the cellular proportions of peripheral blood T cell subsets,ELISA was employed to quantify serum CXCL10 and CXCR3 expression levels before and after treatment.Results After 1 month of taking Chinese medicine,the proportions of CD3+ CD4+ cells and CD3+ CD8+ cells were increased compared before treatment(P＜0.05).The expression level of peripheral serum CXCL10 before treatment was significantly increased compare with the healthy control group(P＜0.01),and the CXCL10 level after treatment was decreased significantly compared with that before treatment(P＜0.05).The expression level of peripheral serum CXCR3 was significantly increased compared with the healthy control group(P＜0.05),while which after treatment was still significantly higher than that in the healthy control group(P＜0.05).Conclusion CXCL10,CXCR3 and T cell subsets proportion may be involved in the pathogenesis of vitiligo.The compound Chinese medicine used in this study plays the curative effect possibly by regulating T cell subsets and expression levels of CXCL10 and CXCR3.

Relationship between subtypes of T follicular helper cells and unexplained recurrent spontaneous abortion / 上海交通大学学报（医学版）

Objective · To discuss the relationship between unexplained recurrent spontaneous abortion (URSA) and T follicular helper (Tfh) cell subtypes. Methods · Twenty-eight normal early pregnancy women, who had undergone induced abortion, were taken as control, and 28 patients with URSA were enrolled in the abortion group. The mononuclear cells in peripheral blood and decidual tissues were separated in the two groups, and CXCR3+CCR6- Tfh cells, CXCR3-CCR6- Tfh cells, CXCR3-CCR6+ Tfh cells and B cells were tested by flow cytometry. Results · The decidual CXCR3-CCR6- Tfh cells significantly increased in the abortion group compared with control group (P=0.015). And there was a strong association between the decidual CXCR3-CCR6- Tfh cells and B cells in URSA patients (R2=0.779, P=0.025). Conclusion · The up-regulation of decidual CXCR3-CCR6- Tfh cells in early pregnancy women may be related with the occurrence of URSA.

Relationship between subtypes of T follicular helper cells and unexplained recurrent spontaneous abortion / 上海交通大学学报（医学版）

Objective · To discuss the relationship between unexplained recurrent spontaneous abortion (URSA) and T follicular helper (Tfh) cell subtypes. Methods · Twenty-eight normal early pregnancy women, who had undergone induced abortion, were taken as control, and 28 patients with URSA were enrolled in the abortion group. The mononuclear cells in peripheral blood and decidual tissues were separated in the two groups, and CXCR3+CCR6- Tfh cells, CXCR3-CCR6- Tfh cells, CXCR3-CCR6+ Tfh cells and B cells were tested by flow cytometry. Results · The decidual CXCR3-CCR6- Tfh cells significantly increased in the abortion group compared with control group (P=0.015). And there was a strong association between the decidual CXCR3-CCR6- Tfh cells and B cells in URSA patients (R2=0.779, P=0.025). Conclusion · The up-regulation of decidual CXCR3-CCR6- Tfh cells in early pregnancy women may be related with the occurrence of URSA.

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.

The protactive effects and mechanisms of cx3cr1 antibody on retinal neuron in rats with ischemia reperfusion injury by intravitreal injection / 中华实验眼科杂志

Background Study confirmed that the active microglia may injure retinal ganglion cells (RGCs) in retinal ischemia reperfusion injury (IRI), and increased cx3cr1 expression is an important factor in microglial activation,and thus blocking the expression of cx3cr1 can inhibit microglial activation, which may be useful in neuronal protection.Objective This study was to analyze the protective effects of cx3cr1 antibody on retinal neuron in rat eyes with IRI.Methods Ninety SD rats were divided into 4 groups according to random number table.IRI models were established by perfusing normal saline solution into the anterior chamber.The cx3cr1 antibody of 1 μl (0.2 μg/μl) was intravitreally injected in the right eyes in the normal rats or model rats as the only cx3cr1 antibody injected group and the model cx3cr1 antibody injected group,respectively,and no any drug was injected in the rats of the normal control group and model control group.Retinal sections were prepared 48 hours after modeling, and apoptosis of retinal neutron was observed under the transmission electron microscope;the morphology of retinas was exmined and the number of survival RGCs was calculated by histopathologic method.The expression of CD68 in activated retinal microglial cells was detected by immunochemistry, and the relative expression levels of cx3cr1 mRNA,tumor necrosis factor-α (TNF-ct) mRNA and interleukin-1 β (IL-1 β) mRNA in the retinas were assayed by real time quantitative PCR.Results The cell nucleus of RGCs showed the round and ellipse in shape and there were abundant organelles in the cells.The mophology of photoreceptors was normal with abundant mitochondrions.Irregular cell shape, disrupture of outer segment membranous disc, proliferative microglial cells in RGC layer were seen in the model group.However,these findings were mild in the model cx3crl antibody group.The mean number of survival RGCs was (38.100 ± 3.929), (37.200 ± 5.266), (26.700 ± 2.584) and (31.700 ± 2.946)/field in the normal control group,only cx3cr1 antibody injected group, model control group and model cx3cr1 antibody injected group,showing significant differences between the model group and the normal control group, only cx3cr1 antibody injected group or model cx3cr1 antibody injected group (t =7.492,6.125,-4.607, all at P＜0.01).The expression levels (absorbance) of CD68 in rat retinas were significantly higher in the model group than those in the normal control group, only cx3cr1 antibody injected group and model cx3cr1 antibody injected group (t =-3.397 ,P =0.008;t =-6.207 ,P =0.000;t =3.494, P =0.007).The relative expression levels of cx3cr1 mRNA, TNF-α mRNA and IL-1 β mRNA in rat retinas were raised in the model group compared with the only cx3er1 antibody injected group and model cx3cr1 antibody injected group (all at P＜0.01).No significant differences were observed in these indicators between the normal control group and the only cx3crl antibody injected group (all at P＜0.05).Conclusions Intravitreal injection of cx3cr1 antibody to neutralize cx3cr1 levels in retinas can effectively inhibit the activation of retinal microglia,decrease the release of inflammatory factors, reduce the apoptosis of RGCs and thereby protect the retinal neutrons against IRI in SD rats.Intravitreal injection of cx3cr1 is safe and feasible.

Effect of CXCR3 Overexpression in Vitro on invasion of T Lymphoblastic Leukemia Cells / 实用医学杂志

Objective To explore the invasion effect of CXCR3 overexpression on T lymphoblastic leukemia (Jurkat cells) with chemokine receptors. Methods Mouse CXCR3 was amplified by RT-PCR and overexpressing CXCR3 lentivirus carrying GFP&Puromycin (puro) was constructed. CXCR3 expression on infected Jurkat cells surface was detected by FCM. Constructed cells were seeded in Transwell invasion model to study whether CXCR3 overexpression would increase the invasion or not. Results GFP expression on Jurkat cells was less than 10% after 96 h lentivirus infection. CXCR3 expression was 90% higher than vector group , and GFP expression reached 90% after screening. Therefore, Jurkat cells with stable overexpression of CXCR3 were successfully constructed. Invasion rate of Jurkat CXCR3 cells was [(12.71 ± 1.03)%], which was significant higher than that of vector control group [(6.82 ± 0.49)%], (P < 0.0001). Conclusions CXCR3 expression on leukemia cells is closely associated with leukemia invasion. The increase of CXCR3 expression can enhance the invasion of leukemia cells, and may be one of the mechanisms of T lymphoblastic leukemia invasion.

Effect of IL-4 on the Development and Function of Memory-like CD8 T Cells in the Peripheral Lymphoid Tissues

Unlike conventional T cells, innate CD8 T cells develop a memory-like phenotype in the thymus and immediately respond upon antigen stimulation, similar to memory T cells. The development of innate CD8 T cells in the thymus is known to require IL-4, which upregulates Eomesodermin (Eomes). These features are similar to that of virtual memory CD8 T cells and IL-4-induced memory-like CD8 T cells generated in the peripheral tissues. However, the relationship between these cell types has not been clearly documented. In the present study, IL-4-induced memory-like CD8 T cells generated in the peripheral tissues were compared with innate CD8 T cells in terms of phenotype and function. When an IL-4/anti-IL-4 antibody complex (IL-4C) was injected into C57BL/6 mice daily for 7 days, the Eomes(hi)CXCR3+ CD8 T cell population was markedly increased in the peripheral lymphoid organs and blood. These cells were generated from naïve CD8 T cells or accumulated via the expansion of pre-existing CD44(hi)CXCR3+ CD8 T cells. Initially, the majority of these CXCR3+ CD8 T cells expressed low levels of CD44, which was followed by the conversion to the CD44(hi) phenotype. This conversion was associated with the acquisition of enhanced effector function. After discontinuation of IL-4C treatment, Eomes expression levels gradually decreased in CXCR3+ CD8 T cells. Taken together, the results of this study demonstrate that IL-4-induced memory-like CD8 T cells generated in the peripheral lymphoid tissues are phenotypically and functionally similar to the innate CD8 T cells generated in the thymus.

Is CXCL10/CXCR3 axis overexpression a better indicator of leprosy type 1 reaction than inducible nitric oxide synthase.

Background & objectives: Leprosy type 1 reactions (T1R) are acute episodes of immune exacerbation that are a major cause of inflammation and nerve damage. T1R are diagnosed clinically and supported by histopathology. No laboratory marker is currently available that can accurately predict a T1R. Increased plasma and tissue expression of inducible nitric oxide synthase (i-NOS) and chemokine CXCL10 have been demonstrated in T1R. We studied the gene expression and immunoexpression of i-NOS, CXCL10 and its receptor CXCR3 in clinically and histopathologically confirmed patients with T1R and compared with non-reactional leprosy patients to understand which biomarker has better potential in distinguishing reaction from non-reaction. Methods: Gene expression of i-NOS, CXCL10 and CXCR3 was studied in 30 skin biopsies obtained from patients with borderline tuberculoid (BT), mid-borderline (BB) and borderline lepromatous (BL) leprosy with and without T1R by real-time PCR. Further validation was done by immunhistochemical expression on 60 borderline leprosy biopsies with and without T1R. Results: Of the 120 patients histopathological evaluation confirmed T1R in 65 (54.2%) patients. CXCR3 gene expression was significantly (P<0.05) higher in BT- and BB-T1R patients compared to those without T1R. The CXCL10 gene expression was significantly higher (P<0.05) in BB leprosy with T1R but the difference was not significant in patients with BT with or without T1R. Immunoexpression for CXCR3 was significant in both BB-T1R and BB (P<0.001) and BT and BT-T1R (P<0.001). Immunoexpression of CXL10 was significant only in differentiating BB from BB-T1R leprosy (P<0.01) and not the BT cases. i-NOS immunoexpression was not useful in differentiating reactional from non-reactional leprosy. Interpretation & conclusions: Both CXCL10 and CXCR3 appeared to be useful in differentiating T1R reaction in borderline leprosy while CXCR3 alone differentiated BT from BT-T1R. CXCR3 may be a potentially useful immunohistochemical marker to predict an impending T1R.

Silibinin, up-regulates chemokine receptor expression in MDA-MB-231 breast cancer cell line.

Introduction: Silibinin, a polyphenolic flavonoid isolated from the milk thistle plant (Silybummarianum), has various applications in cancer therapy. This investigation aimed to examine the effects of silibinin on proliferation and chemokine receptor expression on MDA-MB-231 cells, a highly metastatic human breast cancer cell line. Methods: The cytotoxic effect of silibinin on MDA-MB-231 cells was determined by micro-culture tetrazolium test (MTT) assay. In addition, the expression of chemokine receptors CXCR3, CCR5 and CCR7 genes in response to silibinin was evaluated by Real-Time PCR. Results: Data analysis from MTT assay showed that silibinin had dose-dependent and time-dependent inhibitory effects on MDA-MB-231 cell line. Moreover, Real-Time PCR analysis showed that silibinin not only had no inhibitory effects on CXCR3, CCR5 and CCR7 gene expressions, but also could increase significantly the expression of these genes in a dose and time-dependent manner. Conclusion: These results revealed for the first time the increased possibility of CXCR3, CCR5 and CCR7 genes expression in response to silibinin in human breast cancer cells.

Role of CXCL10 in pathogenesis of hepatitis C and antiviral therapy / 临床肝胆病杂志

Hepatitis C virus (HCV) infection represents an important public health problem worldwide. Eradicating HCV can finally delay or prevent the progression of HCV infection to end-stage liver diseases such as liver cirrhosis and liver cancer. Chemokine (C-X-C motif) ligand 10 (CXCL10) is a chemokine belonging to the CXC chemokine family, and it exerts its function through binding to chemokine (C-X-C motif) receptor 3 (CXCR3), playing a critical role in eradication of HCV. This article reviews the relationship of CXCL10 with the pathogenesis of HCV and the effectiveness of antiviral treatment, as well as the CXCL10 measurements. Meanwhile, this article introduces the clinical value of CXCL10 in assessing the risk of liver fibrosis and liver cancer. Further studies are needed to investigate the association between CXCL10 and liver diseases, and CXCL10 may provide a new therapeutic strategy for HCV infection.

Clinical significance of CXCL10 and CXCR3 expression in patients with bladder neoplasm / 重庆医学

Objective To study the expression of CXCL10 and its receptor CXCR3 expression in bladder neoplasm and ex-plore their clinical significance.Methods Totally 80 patients with bladder neoplasm and 33 healthy control were recruited in this study.The serum level of CXCL10 was determined by ELISA and CXCR3 mRNA in peripheral blood mononuclear cell was meas-ured by RT-PCR.The relationship of serum CXCL10 and CXCR3 levels with clinical parameter were analyzed.Results The serum CXCL10 and CXCR3 levels in patients of bladder neoplasm were significantly higher than the control group(P >0.05).The serum CXCL10 and CXCR3 levels was significantly correlated with lymphatic metastasis (P <0.05).Conclusion High expression of CX-CL10 and CXCR3 may relate to bladder cancer and possibly correlate with lymphatic metastasis.

Effect of Genistein combined with cyclosporine A on CXCR3 in rejection of cardiac allograft / 中国免疫学杂志

Objective:To investigate the effect of Genistein combined with cyclosporine A on chemokine receptor CXCR3 in rejection of cardiac allograft in rats.Methods:Heterotopic cervical heart transplantation was performed from Wistar rats to SD rats by using cuff-technique.The SD rat recipients were randomly divided into 3 groups.No treatment was adopted in the acute rejection( AR) group.Rats in the cyclosporine A(CsA) group were treated with cyclosporine A after transplantion.Rats in CsA+Genistein(C+G) group were treated with Genistein combined with cyclosporine A after transplantion.All the cardiac allografts were harvested at 7th day, and made into tissue slices.The HE-staining was used to observe the pathology changes of the allograft myocardia.And the expression of CXCR3 was detected with immunehistochemistry and Western blot.Results:The expression of CXCR3 strongly positively expressed in AR group.The degree of myocardial inflammation in C+G group and the expression of CXCR3 were much lower than the other two groups.Conclusion:Genistein combined with cyclosporine A can significantly relieve rejection of cardiac allograft by inhibiting the ex-pression of CXCR3.

Avaliação do papel da imunidade adaptativa na obesidade: estudo experimental em animais / Evaluation of the role of adaptative immunity in obesity: study in animals

O desenvolvimento gradual e recente de uma epidemia mundial de obesidade alavancou sobremaneira o estudo dessa condição e de suas comorbidades metabólicas. No âmbito fisiopatológico, múltiplos estudos demonstraram a expressão aumentada de mediadores inflamatórios no tecido adiposo de animais e humanos obesos, o acúmulo local de macrófagos, e um papel central da inflamação no desequilíbrio da homeostase metabólica local e sistêmica na obesidade. A definição de um papel ativo dos macrófagos, e portanto da imunidade inata, na rede inflamatória do tecido adiposo, evocou a hipótese de que, similarmente a outras condições inflamatórias crônicas como a aterosclerose, a obesidade também contaria com a importante participação de elementos da imunidade adaptativa, como as células T e suas citocinas, em sua fisiopatologia. Com base nessas considerações, os objetivos principais desse estudo foram: 1) avaliar a presença das células T e o papel do interferon-gama (IFNy), clássica citocina T-helper 1 (ou Th1), na inflamação do tecido adiposo; e 2) estudar mecanismos de acúmulo das células T no tecido adiposo na obesidade, particularmente a participação do receptor CXCR3 nesse processo. Experimentos de citometria de fluxo mostraram que o tecido adiposo visceral de camundongos C57BL/6 obesos após consumo de dieta rica em gorduras apresentou maior número de macrófagos e também de células T, CD4+ e CD8+, em comparação a controles que receberam dieta pobre em gorduras. A expressão de I-Ab, marcador do complexo de histocompatibilidade principal classe II (MHC II) murino, também foi maior no tecido adiposo dos animais obesos, sugerindo a presença local da atividade de apresentação de antígeno com consequente ativação das células T. Quando estimuladas in vitro, células T derivadas do tecido adiposo de camundongos obesos produziram mais IFNy do que aquelas isoladas de controles, novamente sugerindo a ativação dessas células em um contexto de obesidade. Na análise das possíveis...

The gradual and recent development of a worldwide epidemic of obesity greatly leveraged the study of this condition and its metabolic comorbidities. In the pathophysiologic context, multiple studies have demonstrated increased expression of inflammatory mediators in adipose tissue of obese animals and humans, the local macrophage accumulation, and a central role of inflammation in the imbalance of local or systemic metabolic homeostasis in obesity. The concept of an active role of macrophages and thus of innate immunity in the inflammatory network of adipose tissue, suggested the hypothesis that, similar to other chronic inflammatory conditions such as atherosclerosis, obesity also count on the participation of important elements of adaptive immunity such as T cells and their cytokines in its pathophysiology. Based on these considerations, the main objectives of this study were: 1) to evaluate the presence of T cells and the role of interferon-gamma (IFNy), classic T-helper 1 (Th1) cytokine, in adipose tissue inflammation, and 2) to study mechanisms of T cell accumulation in adipose tissue in the context of obesity, particularly the involvement of CXCR3 receptor in this process. Flow cytometry experiments showed that the visceral fat tissue of C57BL/6 obese mice fed a high fat diet showed a greater number of macrophages and also T cells, including CD4+ and CD8+ cells, compared to controls fed a low-fat diet. The expression of I-Ab, murine marker of class II major histocompatibility complex (MHC II), was also higher in adipose tissue of obese animals, suggesting the presence of local antigen presentation and consequent T cell activation. When stimulated in vitro, T cells derived from adipose tissue of obese mice produced more IFNy than those isolated from controls, again suggesting the activation of these cells in the context of obesity. In the analysis of possible functions of IFNy in adipose tissue, stimulation of 3T3 -L1 cells differentiated into adipocytes...

Changes in expression of CXCR3 in regulatory T cells in renal tissues of mice with renal ischemia-reperfusion injury / 中华麻醉学杂志

Objective To evaluate the changes in the expression of CXCR3 in regulatory T cells (Tregs) in the renal tissues of mice with renal ischemia-reperfusion (I/R) injury .Methods Forty-eight SPF male C57BL/6J mice ,aged 8-12 yr ,weighing 20-25 g ,were randomly divided into 3 groups ( n=16 each ) using a random number table:sham operation group (group S) ,group I/R and CD25 monoclonal antibody PC61 group (group P) . Bilateral kidneys were exposed and their pedicles were occluded for 45 min with atraumatic mini-clamp followed by 72 h reperfusion .PC61 250 μg was injected intraperitoneally at 24 h before the model was established .Blood samples were collected from the inferior vena cava at 24 and 72 h of reperfusion (T1 ,2 ) for determination of serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations .Bilateral kidneys were obtained for determination of CD4+ CD25+ Foxp3+ Treg count and CXCR3+ CD4+ CD25+ Foxp3+ Treg count in renal tissues and the pathological changes of the kidney were scored .Results Compared with group S , the serum BUN and Cr concentrations and pathological scores were significantly increased at T1 ,2 in I/R and P groups ,and the number of CD4+ CD25+ Foxp3+ Treg and CXCR3+ CD4+ CD25+ Foxp3+ Treg was increased at T2 in I/R group ( P<0.05) .Compared with group I/R ,the serum BUN and Cr concentrations and pathological scores were significantly increased at T2 ,and the number of CD4+ CD25+ Foxp3+ Treg and CXCR3+ CD4+ CD25+ Foxp3+ Treg was decreased at T2 in P group ( P<0.05 ) .Conclusion Up-regulation of CXCR3 is helpful in migration of Tregs into the renal tissues of mice with renal I/R injury .