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- Title
The Dichotomous Pattern of IL-12R and IL-23R Expression Elucidates the Role of IL-12 and IL-23 in Inflammation.
- Authors
Chognard, Gaëlle; Bellemare, Lisa; Pelletier, Adam-Nicolas; Dominguez-Punaro, Maria C.; Beauchamp, Claudine; Guyon, Marie-Josée; Charron, Guy; Morin, Nicolas; Sivanesan, Durga; Kuchroo, Vijay; Xavier, Ramnik; Michnick, Stephen W.; Chemtob, Sylvain; Rioux, John D.; Lesage, Sylvie
- 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.
- Subjects
INTERLEUKINS; GENE expression; INFLAMMATION; CYTOKINES; KILLER cells; LYMPHOID tissue; LABORATORY mice
- Publication
PLoS ONE, 2014, Vol 9, Issue 2, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0089092