Hyperactivation and enhanced cytotoxicity of reduced CD8+ gamma delta T cells in the intestine of patients with Crohn's disease correlates with disease activity.

BACKGROUND AND AIMS: We aimed to investigate the immune characteristics of intestinal CD8+ gamma delta T (CD8+ γδ T) cells in Crohn's disease (CD) and their correlation with disease activity. METHODS: The study cohorts included 21 CD patients and 21 healthy individuals. CD8+ γδ T cells were isolated from human ileal mucosa for detection by flow cytometry. The activation or inhibition status of cells was detected by detecting the expression of activation marker HLA-DR and the immunosuppressive molecule PD-1 on cells. The cytotoxicity of cells was assessed by detecting the expression of cytotoxic molecules (Perforin, Granzyme B, and TRAIL) in cells. Ratios of investigated cells were calculated as prediction factors by receiver operating characteristic curve (ROC) analysis. RESULTS: The study revealed a reduction in intestinal CD8+ γδT cells among active CD patients, with a more pronounced reduction observed in moderately active patients compared to mildly active patients. Moreover, active CD patients exhibited heightened activation levels in their intestinal CD8+ γδT cells, whereas the activation was comparatively weakened in moderately active patients compared with mildly active patients. Additionally, the cytotoxicity of intestinal CD8+ γδT cells was enhanced solely in mildly active patients, while it was impaired in moderately active patients compared with mildly active patients. Furthermore, HLA-DR+ CD8+ γδT cell ratio, CD8+ γδT ratio, and CD8+ γδT count were identified as indicators in the diagnosis of active CD. Meanwhile, the ratios of Granzyme B+ CD8+ γδT cell and Perforin+ CD8+ γδT cell were identified as indicators that distinguish mildly moderately active CD cases. CONCLUSIONS: Intestinal CD8+ γδT was reduced in active CD patients, but their activation and cytotoxicity were enhanced. However, with increased disease activity, intestinal CD8+ γδ T cells became dysfunctional. CD-specific perturbations observed in various phenotypic markers in CD8+ γδ T cells can be used as indicators to assist in diagnosing CD patients.

Symptomatic Postoperative Discal Pseudocyst After Percutaneous Endoscopic Interlaminar Discectomy: Case Report and Literature Review.

BACKGROUND: A postoperative discal pseudocyst (PDP) is a cystic lesion that is formed in the operation area of the intervertebral disc, leading to recurrence or even worse symptoms. To our knowledge, to date, there is no research focusing specifically on PDP following percutaneous endoscopic interlaminar discectomy (PEID). CASE PRESENTATION: We present the case of a 27-year-old man with L5 S1 intervertebral disc herniation who was treated with PEID after failed conservative treatment. His leg pain was relieved immediately but reoccurred on the 40th day. MRI showed a PDP. Because loxoprofen and bedrest were ineffective and the patient was anxious, we performed a cystectomy. The patient's symptoms were significantly relieved, and a 6-month follow up showed no recurrence both clinically and on MRI. CONCLUSION: A PDP is more likely to form using the interlaminar approach than the transforaminal approach. For patients with mental stress, severe pain, and neurological symptoms, surgery is suggested to remove the cyst. Discectomy cannot be performed when disc degeneration is mild.

High expression of IGFBP7 in fibroblasts induced by colorectal cancer cells is co-regulated by TGF-ß and Wnt signaling in a Smad2/3-Dvl2/3-dependent manner.

Fibroblasts in the tumor microenvironment are a key determinant in cancer progression and may be a promising target for cancer therapy. Insulin-like growth factor binding protein 7 (IGFBP7) is known as a tumor suppressor in colorectal cancer (CRC). The present study investigated the inductive mechanism of IGFBP7 expression in fibroblasts by supernatant from the CRC cell line, SW620. The results showed that the expression of IGFBP7 was up-regulated in the fibroblasts when treated with SW620 supernatant and exogenous TGF-ß1. The IGFBP7 induced by SW620 supernatant or TGF-ß1 was partially inhibited by the TGF-ß1 specific antibody AF and TGF-ß1 receptor antagonist SB431542. The Wnt signaling-targeted genes, c-Myc, CCND1 and the proteins Dvl2/3, were all up-regulated in fibroblasts expressing high levels of IGFBP7, and the up-regulation could be inhibited both by the Wnt signaling antagonist Dickkopf-1 (DKK1) and by the TGF-ß1 receptor antagonist SB431542. In conclusion, CRC cells promote the high expression of IGFBP7 in fibroblasts, most likely through the co-regulation of TGF-ß and Wnt signaling in a Smad2/3-Dvl2/3 dependent manner. Taken together, these data suggest that the fibroblasts could be a novel therapeutic target in tumor therapy.