Deficiency of annexin A1 in CD4+ T cells exacerbates T cell-dependent inflammation.

Authors: Yang, YH  Song, W  Deane, JA  Kao, W  Ooi, JD  Ngo, D  Kitching, AR  Morand, EF  Hickey, MJ 
Citation: Yang YH, etal., J Immunol. 2013 Feb 1;190(3):997-1007. doi: 10.4049/jimmunol.1202236. Epub 2012 Dec 24.
Pubmed: (View Article at PubMed) PMID:23267026
DOI: Full-text: DOI:10.4049/jimmunol.1202236

Annexin A1 (AnxA1) is recognized as an endogenous anti-inflammatory molecule. However, its effects on the adaptive immune response and, in particular, on T cells remain unclear. In this study, we investigated the actions of AnxA1 in three distinct models of T cell-mediated inflammation. In contact hypersensitivity, collagen-induced arthritis, and inflammation induced by OT-II TCR transgenic T cells responding to OVA, AnxA1 deficiency significantly increased Ag-induced T cell proliferation and the resultant level of inflammation. In the contact hypersensitivity model, this was associated with increased adhesion of CD4(+) T cells, CD8(+) T cells, and neutrophils in the dermal microvasculature, as well as increased T cell expression of RORgammat and IL-17A. In collagen-induced arthritis, deficiency of endogenous AnxA1 increased susceptibility to arthritis and Ag-specific T cell activation. Deficiency of AnxA1 also increased OVA-induced cutaneous delayed-type hypersensitivity and IFN-gamma and IL-17 release. Transfer experiments using CD4(+) T cells from AnxA1(-/-) mice demonstrated that the absence of AnxA1 solely in T cells resulted in increased inflammatory responses in wild-type recipients. Similarly, experiments using AnxA1(-/-) OT-II CD4(+) T cells demonstrated that the absence of AnxA1 in T cells was sufficient to induce increased Ag-specific CD4(+) T cell proliferation in vivo, augment T cell production of IFN-gamma, IL-17, TNF, and IL-6, and increase Akt, ERK, and p38 activation. Together, these findings indicate that T cell-expressed AnxA1 functions to attenuate T cell-driven inflammatory responses via T cell-intrinsic effects on intracellular signaling, proliferation, and Th1/Th17 cytokine release.

Annotation

Disease Annotations
Objects Annotated

Additional Information

 
CRRD Object Information
CRRD ID: 7421573
Created: 2013-11-21
Species: All species
Last Modified: 2013-11-21
Status: ACTIVE



NHLBI Logo

RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.