MiR-155 Promotes T Follicular Helper Cell Accumulation During Chronic, Low-grade Inflammation

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2014 Nov 5

PMID 25367574

Citations 98

Authors

Ruozhen Hu

Dominique A Kagele

Thomas B Huffaker

Marah C Runtsch

Margaret Alexander

Jin Liu

Erin Bake

Wei Su

Matthew A Williams

Dinesh S Rao

Thomas Moller

Gwenn A Garden

June L Round

Ryan M OConnell

Affiliations

Soon will be listed here.

Abstract

Chronic inflammation is a contributing factor to most life-shortening human diseases. However, the molecular and cellular mechanisms that sustain chronic inflammatory responses remain poorly understood, making it difficult to treat this deleterious condition. Using a mouse model of age-dependent inflammation that results from a deficiency in miR-146a, we demonstrate that miR-155 contributed to the progressive inflammatory disease that emerged as Mir146a(-/-) mice grew older. Upon analyzing lymphocytes from inflamed versus healthy middle-aged mice, we found elevated numbers of T follicular helper (Tfh) cells, germinal center (GC) B cells, and autoantibodies, all occurring in a miR-155-dependent manner. Further, Cd4-cre Mir155(fl/fl) mice were generated and demonstrated that miR-155 functions in T cells, in addition to its established role in B cells, to promote humoral immunity in a variety of contexts. Taken together, our study discovers that miR-146a and miR-155 counterregulate Tfh cell development that drives aberrant GC reactions during chronic inflammation.

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