TY - JOUR
T1 - Circulating and gut-resident human Th17 cells express CD161 and promote intestinal inflammation
AU - Kleinschek, Melanie A.
AU - Boniface, Katia
AU - Sadekova, Svetlana
AU - Grein, Jeff
AU - Murphy, Erin E.
AU - Turner, Scott P.
AU - Raskin, Lisa
AU - Desai, Bela
AU - Faubion, William A.
AU - De Malefyt, Rene Waal
AU - Pierce, Robert H.
AU - McClanahan, Terrill
AU - Kastelein, Robert A.
PY - 2009/3/16
Y1 - 2009/3/16
N2 - The C-type lectin-like receptor CD161, which has recently been described to promote T cell expansion, is expressed on a discrete subset of human CD4 T cells. The function of such cells, however, has remained elusive. We now demonstrate that CD161 + CD4 T cells comprise a circulating and gut-resident T helper 17 (Th17) cell population. During Crohn ' s disease (CD), these CD161 + cells display an activated Th17 phenotype, as indicated by increased expression of interleukin (IL)-17, IL-22, and IL-23 receptor. CD161 + CD4 T cells from CD patients readily produce IL-17 and interferon γ upon stimulation with IL-23, whereas, in healthy subjects, priming by additional inflammatory stimuli such as IL-1β was required to enable IL-23-induced cytokine release. Circulating CD161 + Th17 cells are imprinted for gut homing, as indicated by high levels of CC chemokine receptor 6 and integrin |β7 expression. Supporting their colitogenic phenotype, CD161 + Th17 cells were found in increased numbers in the inflammatory infiltrate of CD lesions and induced expression of inflammatory mediators by intestinal cells. Our data identify CD161 + CD4 T cells as a resting Th17 pool that can be activated by IL-23 and mediate destructive tissue inflammation.
AB - The C-type lectin-like receptor CD161, which has recently been described to promote T cell expansion, is expressed on a discrete subset of human CD4 T cells. The function of such cells, however, has remained elusive. We now demonstrate that CD161 + CD4 T cells comprise a circulating and gut-resident T helper 17 (Th17) cell population. During Crohn ' s disease (CD), these CD161 + cells display an activated Th17 phenotype, as indicated by increased expression of interleukin (IL)-17, IL-22, and IL-23 receptor. CD161 + CD4 T cells from CD patients readily produce IL-17 and interferon γ upon stimulation with IL-23, whereas, in healthy subjects, priming by additional inflammatory stimuli such as IL-1β was required to enable IL-23-induced cytokine release. Circulating CD161 + Th17 cells are imprinted for gut homing, as indicated by high levels of CC chemokine receptor 6 and integrin |β7 expression. Supporting their colitogenic phenotype, CD161 + Th17 cells were found in increased numbers in the inflammatory infiltrate of CD lesions and induced expression of inflammatory mediators by intestinal cells. Our data identify CD161 + CD4 T cells as a resting Th17 pool that can be activated by IL-23 and mediate destructive tissue inflammation.
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U2 - 10.1084/jem.20081712
DO - 10.1084/jem.20081712
M3 - Article
C2 - 19273624
AN - SCOPUS:63449133361
SN - 0022-1007
VL - 206
SP - 525
EP - 534
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 3
ER -