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Cutting Edge: Vasoactive Intestinal Peptide (VIP) Induces Differentiation of Th17 Cells with a Distinctive Cytokine Profile¹

Department of Medicine and Department of Microbiology-Immunology, University of California Medical Center, San Francisco, CA 94143

Immune cellular effects of vasoactive intestinal peptide (VIP) are transduced by VIP G protein-coupled receptors type 1 (VPAC₁) and type 2 (VPAC₂). We now show that VIP with TGFβ stimulates the transformation of CD4 T cells to a distinctive type of Th17 cell that generates IL-17 but not IL-6 or IL-21. VIP induction of Th17 cells was higher in VPAC₂ knockout mice than wild-type mice, suggesting that VPAC₁ is the principal transducer. Compared with Th17 cells elicited by IL-6, those evoked by VIP were similar in the secretion of IL-17 and IL-22, but lacked IL-21 secretion. Suppression of VIP induction of Th17 cells by protein kinase A inhibitors and enhancement by pharmacologically increased cAMP supports a role for this signal. The ability of VIP-VPAC₁ axis signals to evoke development of a novel type of Th17 cells demonstrates the unique specificity of neuroregulatory mechanisms in the immunological environment.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grant R0-1 AI29912.

² Address correspondence and reprint requests to Dr. Edward J. Goetzl, University of California, Room UB8B, UC Box 0711, 533 Parnassus at Fourth Avenue, San Francisco, CA 94143-0711. E-mail address: edward.goetzl{at}ucsf.edu

³ Abbreviations used in this paper: VIP, vasoactive intestinal peptide; a-TCR, anti-CD3 and anti-CD28 Ab; MS, multiple sclerosis; PKA, protein kinase A; VPAC₁, VIP type 1 receptor; VPAC₂, VIP type 2 receptor; WT, wild type.