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Vasoactive intestinal peptide (VIP) induces differentiation of unique Th17 cells independently of IL‐6 and IL‐21
Author(s) -
Yadav Mahesh,
Rosenbaum Jennifer,
Goetzl Edward
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.663.4
Subject(s) - vasoactive intestinal peptide , cyclic adenosine monophosphate , immune system , microbiology and biotechnology , receptor , secretion , biology , endocrinology , medicine , chemistry , immunology , neuropeptide
Vasoactive intestinal peptide (VIP) effects on many immune functions are transduced by VIP G‐protein‐coupled receptors type 1 (VPAC1) and type 2 (VPAC2) on immune cells. The Th17 subset of CD4 T helper cells that develops under the control of transforming growth factor‐beta (TGFβ) and interleukin (IL)‐6 mediates local tissue and systemic inflammation through IL‐17, IL‐6, IL‐21 and IL‐22. We now show that VIP in the presence of TGFβ stimulates development of a distinctive type of Th17 cell that generates IL‐17, but not IL‐6 or IL‐21. That the level of VIP‐induced Th17 cells was higher in VPAC2 knockout mice, whose CD4 T cells express only VPAC1, suggests VPAC1 is the principal transducer of VIP effects. Th17 cells elicited by VIP and by IL‐6 were similar in their capacity to secrete IL‐17 and IL‐22, but only the IL‐6‐elicited Th17 cells secreted IL‐21. Suppression of VIP‐induced Th17 cell differentiation by protein kinase A inhibitors and the induction of similar Th17 cells by phosphodiesterase inhibition supports a critical signaling role for increases in 3′‐5′‐cyclic adenosine monophosphate (cAMP). The novel ability of VIP‐VPAC1 axis signals to evoke IL‐6‐independent development of a distinct type of Th17 cells demonstrates the unique specificity of neuroregulatory mechanisms in the immunological environment