γδ T Cells Enhance Autoimmunity by Restraining Regulatory T Cell Responses via an Interleukin-23-Dependent Mechanism

Mice that lack interleukin-23 (IL-23) are resistant to T cell-mediated autoimmunity. Although IL-23 is a maturation factor for T helper 17 (Th17) cells, a subset of γδ T cells expresses the IL-23 receptor (IL-23R) constitutively. Using IL-23R reporter mice, we showed that γδ T cells were the first c...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2010-09, Vol.33 (3), p.351-363
Main Authors: Petermann, Franziska, Rothhammer, Veit, Claussen, Malte C., Haas, Jan D., Blanco, Lorena Riol, Heink, Sylvia, Prinz, Immo, Hemmer, Bernhard, Kuchroo, Vijay K., Oukka, Mohamed, Korn, Thomas
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Autoimmunity
Encephalomyelitis, Autoimmune, Experimental - etiology
Interleukin-17 - biosynthesis
Interleukin-22
Interleukin-23 - physiology
Interleukins - biosynthesis
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Receptors, Antigen, T-Cell - physiology
Receptors, Antigen, T-Cell, gamma-delta - physiology
Receptors, Interleukin - physiology
T-Lymphocytes, Regulatory - immunology
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Summary:Mice that lack interleukin-23 (IL-23) are resistant to T cell-mediated autoimmunity. Although IL-23 is a maturation factor for T helper 17 (Th17) cells, a subset of γδ T cells expresses the IL-23 receptor (IL-23R) constitutively. Using IL-23R reporter mice, we showed that γδ T cells were the first cells to respond to IL-23 during experimental autoimmune encephalomyelitis (EAE). Although γδ T cells produced Th17 cell-associated cytokines in response to IL-23, their major function was to prevent the development of regulatory T (Treg) cell responses. IL-23-activated γδ T cells rendered αβ effector T cells refractory to the suppressive activity of Treg cells and also prevented the conversion of conventional T cells into Foxp3 + Treg cells in vivo. Thus, IL-23, which by itself has no direct effect on Treg cells, is able to disarm Treg cell responses and promote antigen-specific effector T cell responses via activating γδ T cells. ► IL-23R is constitutively expressed in a subset of γδ T cells ► IL-23R + γδ T cells accumulate in the CNS during EAE ► IL-23-activated γδ T cells suppress conversion of naive T cells into Treg cells ► IL-23-activated γδ T cells inhibit Treg cell responses in vivo
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2010.08.013