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- Title
Adiponectin is a negative regulator of antigen-activated T cells.
- Authors
Wilk, Sabrina; Scheibenbogen, Carmen; Bauer, Sandra; Jenke, Alexander; Rother, Madlen; Guerreiro, Manuel; Kudernatsch, Robert; Goerner, Nicole; Poller, Wolfgang; Elligsen-Merkel, Diana; Utku, Nalan; Magrane, Jordi; Volk, Hans D.; Skurk, Carsten
- Abstract
Adiponectin (APN), a cytokine constitutively produced in fat tissue, has been shown to exert anti-inflammatory effects in various disease models. While the influence of APN on monocytic cells has been extensively studied in vitro, little is known about its role in T cells. In this study, we show that while <10% of human peripheral blood T cells express adiponectin receptors (AdipoRs) on their surface, most T cells store AdipoRs in intracellular compartments. AdipoRs colocalized with immune regulatory molecules CTLA-4 and TIRC7 within clathrin-coated vesicles. After stimulation, the expression of adiponectin receptor 1 (AdipoR1) and AdipoR2 was upregulated on the surface of antigen-specific T cells, as determined by tetramer or CD137 staining, and AdipoR1 and AdipoR2 coexpressed with CTLA-4. Addition of APN resulted in a significant diminution of antigen-specific T-cell expansion. Mechanistically, APN enhanced apoptosis and inhibited proliferation of antigen-specific T-cell lines. Further, APN directly inhibited cytokine production in response to antigen stimulation. In line with the in vitro data, APN-deficient (knockout, KO) mice had higher frequencies of CD137+ T cells upon Coxsackie B virus infection. Altogether, our data suggest that APN is a novel negative T-cell regulator. In contrast to the CTLA-4 ligand B7 only expressed on APCs, APN is abundant in human plasma.
- Publication
European Journal of Immunology, 2011, Vol 41, Issue 8, p2323
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.201041349