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

Melanie A. Kleinschek, Katia Boniface, Svetlana Sadekova, Jeff Grein, Erin E. Murphy, Scott P. Turner, Lisa Raskin, Bela Desai, William A. Faubion, Rene Waal De Malefyt, Robert H. Pierce, Terrill McClanahan, Robert A. Kastelein

Research output: Contribution to journalArticlepeer-review

340 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)525-534
Number of pages10
JournalJournal of Experimental Medicine
Issue number3
StatePublished - Mar 16 2009

ASJC Scopus subject areas

  • Medicine(all)


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