Absence of MHC class II on cDCs results in microbialdependent intestinal inflammation

Jakob Loschko, Heidi A. Schreiber, Gereon J. Rieke, Daria Esterházy, Matthew M. Meredith, Virginia A. Pedicord, Kai Hui Yao, Silvia Caballero, Eric G. Pamer, Daniel Mucida, Michel C. Nussenzweig

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

Conventional dendritic cells (cDCs) play an essential role in host immunity by initiating adaptive T cell responses and by serving as innate immune sensors. Although both innate and adaptive functions of cDCs are well documented, their relative importance in maintaining immune homeostasis is poorly understood. To examine the significance of cDC-initiated adaptive immunity in maintaining homeostasis, independent of their innate activities, we generated a cDC-specific Cre mouse and crossed it to a floxed MHC class II (MHC II) mouse. Absence of MHC II on cDCs resulted in chronic intestinal inflammation that was alleviated by antibiotic treatment and entirely averted under germ-free conditions. Uncoupling innate and adaptive functions of cDCs revealed that innate immune functions of cDCs are insufficient to maintain homeostasis and antigen presentation by cDCs is essential for a mutualistic relationship between the host and intestinal bacteria.

Original languageEnglish (US)
Pages (from-to)517-534
Number of pages18
JournalJournal of Experimental Medicine
Volume213
Issue number4
DOIs
StatePublished - Apr 4 2016

Bibliographical note

Funding Information:
We are grateful to members of the Nussenzweig laboratory for helpful discussion, reagents, and critical reading of the manuscript. This work was supported in part by National Institutes of Health grant number AI 13013. M.C. Nussenzweig is a Howard Hughes Medical Institute investigator. The authors declare no competing financial interests.

Funding Information:
This work was supported in part by National Institutes of Health grant number AI 13013. M.C. Nussenzweig is a Howard Hughes Medical Institute investigator. The authors declare no competing financial interests.

Publisher Copyright:
© 2016 Loschko et al.

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