Innate lymphoid cells promote anatomical containment of lymphoid-resident commensal bacteria

Gregory F. Sonnenberg, Laurel A. Monticelli, Theresa Alenghat, Thomas C. Fung, Natalie A. Hutnick, Jun Kunisawa, Naoko Shibata, Stephanie Grunberg, Rohini Sinha, Adam M. Zahm, Mélanie R. Tardif, Taheri Sathaliyawala, Masaru Kubota, Donna L. Farber, Ronald G. Collman, Abraham Shaked, Lynette A. Fouser, David B. Weiner, Philippe A. Tessier, Joshua R. FriedmanHiroshi Kiyono, Frederic D. Bushman, Kyong Mi Chang, David Artis

Research output: Contribution to journalArticlepeer-review

482 Citations (Scopus)

Abstract

The mammalian intestinal tract is colonized by trillions of beneficial commensal bacteria that are anatomically restricted to specific niches. However, the mechanisms that regulate anatomical containment remain unclear. Here, we show that interleukin-22 (IL-22)-producing innate lymphoid cells (ILCs) are present in intestinal tissues of healthy mammals. Depletion of ILCs resulted in peripheral dissemination of commensal bacteria and systemic inflammation, which was prevented by administration of IL-22. Disseminating bacteria were identified as Alcaligenes species originating from host lymphoid tissues. Alcaligenes was sufficient to promote systemic inflammation after ILC depletion in mice, and Alcaligenes-specific systemic immune responses were associated with Crohn's disease and progressive hepatitis C virus infection in patients. Collectively, these data indicate that ILCs regulate selective containment of lymphoid-resident bacteria to prevent systemic inflammation associated with chronic diseases.

Original languageEnglish
Pages (from-to)1321-1325
Number of pages5
JournalScience
Volume336
Issue number6086
DOIs
Publication statusPublished - 2012 Jun 8
Externally publishedYes

ASJC Scopus subject areas

  • General

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