MiR-155 controls follicular Treg cell-mediated humoral autoimmune intestinal injury by inhibiting CTLA-4 expression

• Published in: International immunopharmacology Vol. 71; pp. 267 - 276
• Main Authors: Chao, Gao, Li, Xiaoli, Ji, Yahong, Zhu, Ying, Li, Na, Zhang, Nana, Feng, Zunyong, Niu, Min
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2019; Elsevier BV
• Subjects: Animals; Antibody Formation; Autoantibodies; Autoantibodies - blood; Autoimmunity; B-Lymphocytes - immunology; Cell activation; Colitis - genetics; CTLA-4; CTLA-4 Antigen - genetics; CTLA-4 Antigen - metabolism; CTLA-4 protein; Dextran; Dextran Sulfate; Disease Models, Animal; Down-Regulation; Follicular regulatory T cell; Foxp3; Foxp3 protein; Germinal Center - immunology; Humans; IBD; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - genetics; Injuries; Intestine; Lymphocyte Activation; Lymphocytes B; Lymphocytes T; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; MicroRNA-155; MicroRNAs - genetics; miRNA; Pathogenesis; Sodium; T-Lymphocytes, Regulatory - immunology; Follicular regulatory T cell; CTLA-4; IBD; Foxp3; MicroRNA-155
• ISSN: 1567-5769; 1878-1705; 1878-1705
• DOI: 10.1016/j.intimp.2019.03.009

High expression levels of miR-155 are involved in the pathogenesis of inflammatory bowel disease (IBD). We observed an increase in miR-155 in peripheral regulatory T (Treg) cells from IBD patients. Mice that specifically overexpress miR-155 in Foxp3+ Treg cells exhibit spontaneous autoimmunity and more severe dextran sulfate sodium (DSS)-induced intestinal injury. MiR-155 overexpression can lead to a lack of follicular Treg (Tfr) cells and central Treg (cTreg), whereas DSS treatment further depletes the Tfr cells. Furthermore, miR-155 can target the expression of CTLA-4 in cTreg and Tfr, directly inhibiting Tfr cell production and promoting enhanced germinal center (GC) B cell activation and autoantibody overproduction. This outcome may be the cause of severe intestinal injury in patients with autoimmune IBD. •Increased levels of miR-155 are found in Treg cells of patients with IBD.•Rosa26miR-155Foxp3Cre mice exhibit autoimmune-induced and aggravated DSS-induced colitis.•miR-155 can be targeted to inhibit CTLA-4 expression in Tfr cells.