title: IL-12p35 subunit contributes to autoimmunity by limiting IL-27-driven regulatory responses.
abstract: Contrasting results have emerged from studies performed using IL-12p35(-/-) mice. Animals lacking the IL-12p35 subunit can either be protected from or develop exacerbated autoimmune diseases, intracellular infections, and delayed-type hypersensitivity responses. In this study, we report that mice lacking the IL-12p35 subunit develop a significantly milder Ag-induced arthritis compared with wild-type (WT) mice. Lack of severe inflammation is accompanied by an increase in the mRNA levels of the Ebi-3 and p28 subunits and increased secretion of IL-27 and IL-10. This anti-inflammatory environment contributed to increased differentiation of regulatory T and B cells with intact suppressive function. Furthermore, IL-12p35(-/-) mice display reduced numbers of Th17 cells compared with WT arthritic mice. Neutralization of IL-27, but not the systemic administration of IL-12, restored inflammation and Th17 to levels seen in WT mice. The restoration of disease phenotype after anti-IL-27 administration indicates that the IL-12p35 subunit acts as negative regulator of the developing IL-27 response in this model of arthritis.
authors.affiliation: Centre for Rheumatology Research, University College London, London WC1E 6JF, United Kingdom.
authors.forename: Rita
authors.initials: R
authors.lastname: Vasconcellos
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Carter
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Rosser
authors.forename: Claudia
authors.initials: C
authors.lastname: Mauri
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D053765:Interleukin-12 Subunit p35 / Q000276:immunology*; D007378:Interleukins / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology
chemical_list: C486767:Il27 protein, mouse; D053765:Interleukin-12 Subunit p35; D007378:Interleukins