title: Adiponectin is a negative regulator of antigen-activated T cells.
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.
authors.affiliation: Institute of Medical Immunology, Charité-Berlin, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Wilk
authors.forename: Carmen
authors.initials: C
authors.lastname: Scheibenbogen
authors.forename: Sandra
authors.initials: S
authors.lastname: Bauer
authors.forename: Alexander
authors.initials: A
authors.lastname: Jenke
authors.forename: Madlen
authors.initials: M
authors.lastname: Rother
authors.forename: Manuel
authors.initials: M
authors.lastname: Guerreiro
authors.forename: Robert
authors.initials: R
authors.lastname: Kudernatsch
authors.forename: Nicole
authors.initials: N
authors.lastname: Goerner
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Poller
authors.forename: Diana
authors.initials: D
authors.lastname: Elligsen-Merkel
authors.forename: Nalan
authors.initials: N
authors.lastname: Utku
authors.forename: Jordi
authors.initials: J
authors.lastname: Magrane
authors.forename: Hans D
authors.initials: HD
authors.lastname: Volk
authors.forename: Carsten
authors.initials: C
authors.lastname: Skurk
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D000818:Animals; D000941:Antigens / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D060908:CTLA-4 Antigen; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D022163:Clathrin-Coated Vesicles / Q000276:immunology / Q000378:metabolism; D003384:Coxsackievirus Infections / Q000235:genetics / Q000276:immunology / Q000821:virology; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D019169:Jurkat Cells; D020014:K562 Cells; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D054419:Receptors, Adiponectin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000276:immunology / Q000378:metabolism
chemical_list: C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; D000941:Antigens; D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D054419:Receptors, Adiponectin; C472421:TCIRG1 protein, human; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D025262:Vacuolar Proton-Translocating ATPases