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 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.
Petermann
Franziska
F
Klinikum rechts der Isar, Department of Neurology, Technical University Munich, Ismaninger Strasse 22, Munich, Germany.
Rothhammer
Veit
V
Claussen
Malte C
MC
Haas
Jan D
JD
Blanco
Lorena Riol
LR
Heink
Sylvia
S
Prinz
Immo
I
Hemmer
Bernhard
B
Kuchroo
Vijay K
VK
Oukka
Mohamed
M
Korn
Thomas
T
D000595:Amino Acid Sequence; D000818:Animals; D015551:Autoimmunity; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology; D020381:Interleukin-17 / Q000096:biosynthesis; D053759:Interleukin-23 / Q000502:physiology*; D007378:Interleukins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000502:physiology*; D018123:Receptors, Interleukin / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D000097043:Interleukin-22
D020381:Interleukin-17; D053759:Interleukin-23; D007378:Interleukins; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018123:Receptors, Interleukin; D000097043:Interleukin-22; C528688:interleukin-23 receptor, mouse