1. Differential cell-intrinsic regulations of germinal center B and T cells by miR-146a and miR-146b.
- Author
-
Cho S, Lee HM, Yu IS, Choi YS, Huang HY, Hashemifar SS, Lin LL, Chen MC, Afanasiev ND, Khan AA, Lin SW, Rudensky AY, Crotty S, and Lu LF
- Subjects
- Animals, Autoantibodies biosynthesis, Autoimmunity genetics, B-Lymphocytes cytology, B-Lymphocytes drug effects, Bone Marrow Cells cytology, Bone Marrow Cells drug effects, Bone Marrow Cells immunology, CD40 Antigens genetics, CD40 Antigens immunology, Cell Differentiation, Gene Expression Regulation, Germinal Center cytology, Germinal Center drug effects, Immunity, Humoral genetics, Interleukin-4 pharmacology, Mice, Mice, Transgenic, MicroRNAs immunology, Primary Cell Culture, Protein Isoforms genetics, Protein Isoforms immunology, T-Lymphocytes, Helper-Inducer cytology, T-Lymphocytes, Helper-Inducer drug effects, B-Lymphocytes immunology, Germinal Center immunology, MicroRNAs genetics, Signal Transduction immunology, T-Lymphocytes, Helper-Inducer immunology
- Abstract
Reciprocal interactions between B and follicular T helper (Tfh) cells orchestrate the germinal center (GC) reaction, a hallmark of humoral immunity. Abnormal GC responses could lead to the production of pathogenic autoantibodies and the development of autoimmunity. Here we show that miR-146a controls GC responses by targeting multiple CD40 signaling pathway components in B cells; by contrast, loss of miR-146a in T cells does not alter humoral responses. However, specific deletion of both miR-146a and its paralog, miR-146b, in T cells increases Tfh cell numbers and enhanced GC reactions. Thus, our data reveal differential cell-intrinsic regulations of GC B and Tfh cells by miR-146a and miR-146b. Together, members of the miR-146 family serve as crucial molecular brakes to coordinately control GC reactions to generate protective humoral responses without eliciting unwanted autoimmunity.
- Published
- 2018
- Full Text
- View/download PDF