MicroRNA regulation of lymphocyte tolerance and autoimmunity
Laura J. Simpson, K. Mark Ansel
Laura J. Simpson, K. Mark Ansel
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Review Series

MicroRNA regulation of lymphocyte tolerance and autoimmunity

Abstract

Understanding the cell-intrinsic cues that permit self-reactivity in lymphocytes, and therefore autoimmunity, requires an understanding of the transcriptional and posttranscriptional regulation of gene expression in these cells. In this Review, we address seminal and recent research on microRNA (miRNA) regulation of central and peripheral tolerance. Human and mouse studies demonstrate that the PI3K pathway is a critical point of miRNA regulation of immune cell development and function that affects the development of autoimmunity. We also discuss how miRNA expression profiling in human autoimmune diseases has inspired mechanistic studies of miRNA function in the pathogenesis of multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes, and asthma.

Authors

Laura J. Simpson, K. Mark Ansel

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Figure 1

miRNAs set thresholds for lymphocyte development.

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miRNAs set thresholds for lymphocyte development. (A) miR-17~92 sets a t...
(A) miR-17~92 sets a threshold for B cell survival during development. miR-17~92 targets several genes in the PI3K pathway, including the proapoptotic molecule BIM. Mice deficient in miR-17~92 in the B cell lineage develop B cell lymphopenia. Mice with overexpression of miR-17~92 in the B cell lineage develop self-reactive B cells. (B) miR-181 sets a threshold for TCR signal strength during T cell development in the thymus. miR-181 expression decreases as thymocytes differentiate from DN to DP to SP thymocytes. miR-181 expression confers greater sensitivity to TCR stimulation by modulating the targets PTPN22, SHP2, DUSP5, DUSP6, and PTEN.