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Regulation and function of IL-17A- and IL-22-producing γδ T cells

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Abstract

The regulation of IL-17A and IL-22 production differs between human and murine γδ T cells. We find that human γδ T cells expressing Vγ2Vδ2 T cell receptors are peripherally polarized to produce IL-17A or IL-22, much like CD4 αβ Th17 T cells. This requires IL-6, IL-1β, and TGF-β, whereas expansion and maintenance requires IL-23, IL-1β, and TGF-β. In contrast, IL-17A and IL-22 production by murine γδ T cells is innately programmed during thymic ontogeny but requires IL-23 and IL-1β for maintenance. Murine γδ cells producing IL-17A and IL-22 play important roles in microbial, autoimmune, and inflammatory responses. However, the roles played by human IL-17A- and IL-22-producing γδ T cells are less clear but are also likely to be important. These observations highlight differences between humans and murine γδ T cells and underscore the importance of IL-17A- and IL-22-producing γδ T cells.

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Abbreviations

APC:

Antigen-presenting cell

AHR:

Aryl hydrocarbon receptor

CIA:

Collagen-induced arthritis

DETC:

Dendritic epidermal T cells

EAE:

Experimental autoimmune encephalomyelitis

FICZ:

6-Formylindolo[3,2-b]carbazole

HMBPP:

(E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate

IL:

Interleukin

IPP:

Isopentenyl pyrophosphate

MHC:

Major histocompatibility complex

MMP:

Matrix metalloproteinase

NKT:

Natural killer T

ROR:

Retinoid-related orphan receptor

STAT:

Signal transducer and activator of transcription

TCR:

T cell antigen receptor

TLR:

Toll-like receptor

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Acknowledgments

We thank Drs. Hong Wang and Grefachew Workalemahu for critical reading of the manuscript. This work was supported by grants to C.T.M. from the National Institute of Arthritis and Musculoskeletal and Skin Disease (AR045504) and the Bill & Melinda Gates Foundation (Exploration OPP1006946). Kristin Ness-Schwickerath was supported by the National Institute of Allergy and Infectious Diseases (T32 AI007511).

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  1. Division of Immunology, Department of Internal Medicine and the Interdisciplinary Graduate Program in Immunology, University of Iowa Carver College of Medicine, EMRB 400F, Iowa City, IA, 52242, USA

    Kristin J. Ness-Schwickerath & Craig T. Morita

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  1. Kristin J. Ness-Schwickerath
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  2. Craig T. Morita
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Correspondence to Craig T. Morita.

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Ness-Schwickerath, K.J., Morita, C.T. Regulation and function of IL-17A- and IL-22-producing γδ T cells. Cell. Mol. Life Sci. 68, 2371–2390 (2011). https://doi.org/10.1007/s00018-011-0700-z

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  • DOI: https://doi.org/10.1007/s00018-011-0700-z

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