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PLoS One. 2014 Feb 21;9(2):e89092. doi: 10.1371/journal.pone.0089092. eCollection 2014.

The dichotomous pattern of IL-12r and IL-23R expression elucidates the role of IL-12 and IL-23 in inflammation.

Author information

1
Research Center, Maisonneuve-Rosemont Hospital, Montréal, Québec, Canada ; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, Québec, Canada.
2
Research Center, Maisonneuve-Rosemont Hospital, Montréal, Québec, Canada.
3
Research Center, Montreal Heart Institute, Montréal, Québec, Canada.
4
Département de Biochimie, Université de Montréal, Montréal, Québec, Canada.
5
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
6
Division of Medical Sciences, Harvard University, Boston, Massachusetts, United States of America.
7
Departments of Pediatrics, Ophthalmology, and Pharmacology, Centre Hospitalier Universitaire Ste-Justine Research Center, Montréal, Québec, Canada.
8
Research Center, Montreal Heart Institute, Montréal, Québec, Canada ; Département de Médicine, Université de Montréal, Montréal, Québec, Canada.

Abstract

IL-12 and IL-23 cytokines respectively drive Th1 and Th17 type responses. Yet, little is known regarding the biology of these receptors. As the IL-12 and IL-23 receptors share a common subunit, it has been assumed that these receptors are co-expressed. Surprisingly, we find that the expression of each of these receptors is restricted to specific cell types, in both mouse and human. Indeed, although IL-12Rβ2 is expressed by NK cells and a subset of γδ T cells, the expression of IL-23R is restricted to specific T cell subsets, a small number of B cells and innate lymphoid cells. By exploiting an IL-12- and IL-23-dependent mouse model of innate inflammation, we demonstrate an intricate interplay between IL-12Rβ2 NK cells and IL-23R innate lymphoid cells with respectively dominant roles in the regulation of systemic versus local inflammatory responses. Together, these findings support an unforeseen lineage-specific dichotomy in the in vivo role of both the IL-12 and IL-23 pathways in pathological inflammatory states, which may allow more accurate dissection of the roles of these receptors in chronic inflammatory diseases in humans.

PMID:
24586521
PMCID:
PMC3931659
DOI:
10.1371/journal.pone.0089092
[Indexed for MEDLINE]
Free PMC Article
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