Local Triggering of the ICOS Coreceptor by CD11c(+) Myeloid Cells Drives Organ Inflammation in Lupus

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2015 Mar 19

PMID 25786178

Citations 27

Authors

Lino L Teichmann

Jaime L Cullen

Michael Kashgarian

Chen Dong

Joe Craft

Mark J Shlomchik

Affiliations

Soon will be listed here.

Abstract

The inducible T cell costimulator (ICOS) is a potent promoter of organ inflammation in murine lupus. ICOS stimulates T follicular helper cell differentiation in lymphoid tissue, suggesting that it might drive autoimmunity by enhancing autoantibody production. Yet the pathogenic relevance of this mechanism remains unclear. It is also unknown whether other ICOS-induced processes might contribute to lupus pathology. Here we show that selective ablation of ICOS ligand (ICOSL) in CD11c(+) cells, but not in B cells, dramatically ameliorates kidney and lung inflammation in lupus-prone MRL.Fas(lpr) mice. Autoantibody formation was largely unaffected by ICOSL deficiency in CD11c(+) cells. However, ICOSL display by CD11c(+) cells in inflamed organs had a nonredundant role in protecting invading T cells from apoptosis by elevating activity of the PI3K-Akt signaling pathway, thereby facilitating T cell accrual. These findings reveal a mechanism that locally sustains organ inflammation in lupus.

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