title: The MicroRNA miR-191 Supports T Cell Survival Following Common γ Chain Signaling.
abstract: To ensure lifelong immunocompetency, naïve and memory T cells must be adequately maintained in the peripheral lymphoid tissues. Homeostatic maintenance of T cells is controlled by tonic signaling through T cell antigen receptors and common γ chain cytokine receptors. In this study, we identify the highly expressed microRNA miR-191 as a key regulator of naïve, memory, and regulatory T cell homeostasis. Conditional deletion of miR-191 using LckCre resulted in preferential loss of peripheral CD4+regulatory T cells as well as naïve and memory CD8+T cells. This preferential loss stemmed from reduced survival following deficient cytokine signaling and STAT5 activation. Mechanistically, insulin receptor substrate 1 (Irs1) is a direct target of miR-191, and dysregulated IRS1 expression antagonizes STAT5 activation. Our study identifies a novel role for microRNAs in fine-tuning immune homeostasis and thereby maintaining the lymphocyte reservoir necessary to mount productive immune responses.
authors.affiliation: From the Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: Erik Allen
authors.initials: EA
authors.lastname: Lykken
authors.affiliation: From the Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710 qi-jing.li@dm.duke.edu.
authors.forename: Qi-Jing
authors.initials: QJ
authors.lastname: Li
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D016923:Cell Death; D002470:Cell Survival; D016207:Cytokines / Q000276:immunology; D017353:Gene Deletion; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000276:immunology; D053631:Interleukin Receptor Common gamma Subunit / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000276:immunology; D041681:NIH 3T3 Cells; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D055504:Insulin Receptor Substrate Proteins; D053631:Interleukin Receptor Common gamma Subunit; C526295:Irs1 protein, mouse; C555937:MIRN191 microRNA, mouse; D035683:MicroRNAs; D011948:Receptors, Antigen, T-Cell
keywords: T cell biology; cell death; cytokine induction; homeostasis; immunodeficiency; microRNA mechanism