![]() In human Tcon, FOXP3 expression is low and transient. Upon T-cell receptor (TCR) engagement, CD25 and, at least in humans, FOXP3 are also upregulated by T-conventional (Tcon) cells. Tregs – CD4 +, but also CD8 + T cells – express the high-affinity IL-2 receptor α-chain (CD25) and the transcription factor Forkhead box P-3 (FOXP3) which is essential for their development, stability and suppressive function ( 7– 9). To assess frequencies and phenotypes of Tregs is crucial, because they elicit self-tolerance and long-term immune homeostasis, protect from tissue inflammation and exert tissue repair by a variety of mechanisms ( 6). Indeed, it has been observed early on that CD4 +CD25 hi Tregs are less among PBMCs, although the inflamed mucosa of IBD patients then proved to be enriched in Tregs ( 5). One prominent population often evaluated in peripheral blood are T-regulatory cells (Tregs) under the claim that they are diminished in inflammatory diseases. ![]() Direct analysis of cells isolated from the inflamed tissues promises more immediate information, for example whether an underrepresented subpopulation among PBMCs migrates to the tissue to be enriched there or whether this subpopulation is overall lessened upon disease onset. However, how well tissue-based immunopathology is reflected by blood analyses is continuously discussed ( 4). This can be very informative and describe cell markers or subpopulations which are indicative for disease. However, to elicit changes in lymphocyte subsets of patients with inflammatory diseases, often blood samples are analyzed in comparison to healthy controls. For longterm, pro-inflammatory cytokines – mostly secreted by pro-inflammatory T cells – are targeted predominantly by anti-TNF biologicals or JAK inhibitors. Since the aberrant immune response in IBD is idiopathic, corticosteroids and broad immunosuppressants are widely used drugs ( 2). A significant number of CD patients – characterized by transmural granulomatous reactions – require surgery because of refractory e.g. In addition, these patients are threatened by long-term complications including increased susceptibility to colorectal cancer and extra-intestinal manifestations such as arthritis. Patients with IBD suffer from abdominal cramping, diarrhea, rectal bleeding, and weight loss due to local intestinal dysfunction. Current concepts suggest that IBD is caused by multiple factors including genetic predisposition, aberrant immune reactions, altered microbiota, environmental factors and loss of intestinal epithelial barrier function ( 1, 2). Despite extensive research, the pathophysiology underlying IBD remains unclear. A breakdown of tolerance contributes to inflammatory bowel disease (IBD) comprising two major types that are known as Crohn’s disease (CD) and ulcerative colitis (UC). Maintenance of intestinal homeostasis is dependent upon the immune system’s ability to remain tolerant to environmental antigens and commensals while mounting appropriate immune responses to pathogens that utilize the gut as a primary site of entry. Most likely, this is both cause and consequence of intestinal inflammation during CD. Together, these findings suggest a bias towards innate-like pro-inflammatory Tregs and innate-like Tcon, which act with less specific cytotoxicity. In blood of CD patients, not well studied CD4 + and CD8 + subsets of CD16 +CCR6 +CD127 + T cells appeared anew, a phenotype reproducible by incubation of healthy blood T cells with patient blood plasma. Some T-conventional (Tcon) cells tended towards innateness. CD4 +Foxp3 +HLA-DR +TIGIT − and CD4 +Foxp3 +CD56 +, express pro-inflammatory IFN-γ. In vitro assays revealed that those subsets, e.g. However, tissue-repairing Tregs decreased, while enigmatic rare Foxp3 + T-cell subsets appeared upon inflammation. ![]() Chronic inflammation enforced activation, exhaustion and terminal differentiation of CD4 + and CD8 + T cells and an enrichment of CD4 +Foxp3 + cells (Tregs) in inflamed intestine. We compared inflamed and not inflamed tissue areas of bowel resections. ![]() To address disease and tissue-specific alterations, we performed a T cell-centric mass cytometry analysis of peripheral and intestinal lymphocytes from patients with Crohn’s disease (CD) and healthy donor PBMCs. A complex and tissue-specific network of cells including T lymphocytes maintains intestinal homeostasis. ![]()
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