Circulating and gut-resident human Th17 cells express CD161 and promote intestinal inflammation.

Kleinschek, M.A., Boniface, K., Sadekova, S., Grein, J., Murphy, E.E., Turner, S.P., Raskin, L., Desai, B., Faubion, W.A., de Waal Malefyt, R., Pierce, R.H., McClanahan, T., Kastelein, R.A.
Journal   J Exp Med.
Species  
Analytes Measured   IL-17A
Matrix Tested   Cell culture supernatants
Year   2009
Volume   206
Page Numbers   525-34
Application   Cytokines and Chemokines
Abstract
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 gamma upon stimulation with IL-23, whereas, in healthy subjects, priming by additional inflammatory stimuli such as IL-1beta 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 beta7 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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