Chognard, GaëlleBellemare, LisaPelletier, Adam-NicolasDominguez-Punaro, Maria C.Beauchamp, ClaudineGuyon, Marie-JoséeCharron, GuyMorin, NicolasSivanesan, DurgaKuchroo, VijayXavier, RamnikMichnick, Stephen W.Chemtob, SylvainRioux, John D.Lesage, Sylvie2014-03-112014Chognard, G., L. Bellemare, A. Pelletier, M. C. Dominguez-Punaro, C. Beauchamp, M. Guyon, G. Charron, et al. 2014. “The Dichotomous Pattern of IL-12R and IL-23R Expression Elucidates the Role of IL-12 and IL-23 in Inflammation.” PLoS ONE 9 (2): e89092. doi:10.1371/journal.pone.0089092. http://dx.doi.org/10.1371/journal.pone.0089092.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879886IL-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.en-USBiologyImmunologyImmune systemCytokinesImmunityInflammationInnate immunityImmunopathologyModel organismsAnimal modelsMouseMolecular cell biologyGene expressionMedicineClinical immunologyAutoimmune diseasesCrohn diseaseGastroenterology and hepatologyInflammatory bowel diseaseJournal Article2014-03-1110.1371/journal.pone.0089092