title: The dichotomous pattern of IL-12r and IL-23R expression elucidates the role of IL-12 and IL-23 in inflammation.
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.
authors.affiliation: Research Center, Maisonneuve-Rosemont Hospital, Montréal, Québec, Canada ; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Chognard
authors.affiliation: Research Center, Maisonneuve-Rosemont Hospital, Montréal, Québec, Canada ; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Lisa
authors.initials: L
authors.lastname: Bellemare
authors.affiliation: Research Center, Maisonneuve-Rosemont Hospital, Montréal, Québec, Canada ; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Adam-Nicolas
authors.initials: AN
authors.lastname: Pelletier
authors.affiliation: Research Center, Maisonneuve-Rosemont Hospital, Montréal, Québec, Canada.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Dominguez-Punaro
authors.affiliation: Research Center, Montreal Heart Institute, Montréal, Québec, Canada.
authors.forename: Claudine
authors.initials: C
authors.lastname: Beauchamp
authors.affiliation: Research Center, Maisonneuve-Rosemont Hospital, Montréal, Québec, Canada.
authors.forename: Marie-Josée
authors.initials: MJ
authors.lastname: Guyon
authors.affiliation: Research Center, Montreal Heart Institute, Montréal, Québec, Canada.
authors.forename: Guy
authors.initials: G
authors.lastname: Charron
authors.affiliation: Research Center, Montreal Heart Institute, Montréal, Québec, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Morin
authors.affiliation: Département de Biochimie, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Durga
authors.initials: D
authors.lastname: Sivanesan
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Vijay
authors.initials: V
authors.lastname: Kuchroo
authors.affiliation: Division of Medical Sciences, Harvard University, Boston, Massachusetts, United States of America.
authors.forename: Ramnik
authors.initials: R
authors.lastname: Xavier
authors.affiliation: Département de Biochimie, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Michnick
authors.affiliation: Departments of Pediatrics, Ophthalmology, and Pharmacology, Centre Hospitalier Universitaire Ste-Justine Research Center, Montréal, Québec, Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Chemtob
authors.affiliation: Research Center, Montreal Heart Institute, Montréal, Québec, Canada ; Département de Médicine, Université de Montréal, Montréal, Québec, Canada.
authors.forename: John D
authors.initials: JD
authors.lastname: Rioux
authors.affiliation: Research Center, Maisonneuve-Rosemont Hospital, Montréal, Québec, Canada ; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lesage
mesh_terms: D000818:Animals; D016207:Cytokines / Q000097:blood; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005434:Flow Cytometry; D006652:Histological Techniques; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology* / Q000378:metabolism; D053759:Interleukin-23 / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism; D051379:Mice; D018448:Models, Immunological; D018123:Receptors, Interleukin / Q000276:immunology* / Q000378:metabolism; D053707:Receptors, Interleukin-12 / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D017931:DNA Primers; D018076:DNA, Complementary; C508439:IL12RB2 protein, human; D053759:Interleukin-23; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; C528688:interleukin-23 receptor, mouse; D018664:Interleukin-12