Selective decrease in colonic CD56^+ T and CD161^+ T cells in the inflamed mucosa of patients with ulcerative colitis

AIM: To investigate the role of local colonic mucosal NK receptor-positive T (NKR+ T) cells in the regulation of intestinal inflammation, we analyzed the population and function of these cells in ulcerative colitis (UC). METHODS: Colonic mucosal tissues were obtained from colonoscopic biopsies of the descending colon from 96 patients with UC (51 endoscopically uninfl amed, 45 inflamed) and 18 normal controls. Endoscopic appearance and histologic score at the biopsied site were determined by Matts’ classification. A single cell suspension was prepared from each biopsy by collagenase digestion. Two NKR+ T cell subsets, CD56+ (CD56+CD3+) T cells and CD161+ (CD161+CD3+) T cells, were detected by flow cytometric analysis. Intracellular cytokine analysis for anti-in? ammatory cytokine interleukin-10 (IL-10) was performed by in vitro stimulation with phorbol-myristate- acetate (PMA) and ionomycin. RESULTS: CD56+ T cells and CD161+ T cells are present in the normal human colon and account for 6.7% and 21.3% of all mononuclear cells, respectively. The populations of both CD56+ T cells and CD161+ T cells were decreased significantly in the inflamed mucosa of UC. In contrast, the frequency of conventional T cells (CD56-CD3+ cells and CD161-CD3+ cells) was similar among the patient and control groups. The populations of NKR+ T cells were correlated inversely with the severity of infl ammation, which was classif ied according to the endoscopic and histologic Matts’ criteria. Interestingly, approximately 4% of mucosal NKR+ T cells expressing IL-10 were detected by in vitro stimulation with PMA and ionomycin.CONCLUSION: Selective reduction in the population of colonic mucosal NKR+T cells may contribute to the development of intestinal inflammation in UC.

Clinical significance of mucosal suppressors of cytokine signaling 3 expression in ulcerative colitis

AIM:To investigate the clinical significance of mucosal expression of suppressors of cytokine signaling 1 (SOCS1) and SOCS3 in human ulcerative colitis (UC). METHODS:Biopsy specimens for histological analysis and mRNA detection were obtained endoscopically from the rectum of 62 patients with UC (36 men; age 13-76 years). The patients were classified endoscopically according to Matts' grade (grade 1 to 4). Expression of SOCS1 and SOCS3 mRNAs was quantified in samples by competitive reverse transcription-polymerase chain reaction (RT-PCR). GAPDH was used as an internal control for efficiency of RT-PCR and amount of RNA. RESULTS:SOCS3 mRNA expression was significantly higher in inflamed mucosa of UC than in inactive mucosa. The level of expression was well correlated with the degree of both endoscopic and histologic inflammation. Interestingly,among the patients in remission,the group with relatively low expression of SOCS3 showed a higher rate of remission maintenance over a 12-mo period. In contrast,SOCS1 mRNA was expressed in both inflamed and non-inflamed colonic mucosa and was not correlated with the activity of colonic mucosa or prognosis. CONCLUSION:These observations suggest that increased expression of mucosal SOCS3,but not of SOCS1,may play a critical role in the development of the colonic inflammation of UC.