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.
CITATION STYLE
Vasconcellos, R., Carter, N. A., Rosser, E. C., & Mauri, C. (2011). IL-12p35 Subunit Contributes to Autoimmunity by Limiting IL-27–Driven Regulatory Responses. The Journal of Immunology, 187(6), 3402–3412. https://doi.org/10.4049/jimmunol.1100224
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