| First Author | Vasconcellos R | Year | 2011 |
| Journal | J Immunol | Volume | 187 |
| Issue | 6 | Pages | 3402-12 |
| PubMed ID | 21844391 | Mgi Jnum | J:179241 |
| Mgi Id | MGI:5301495 | Doi | 10.4049/jimmunol.1100224 |
| Citation | Vasconcellos R, et al. (2011) IL-12p35 subunit contributes to autoimmunity by limiting IL-27-driven regulatory responses. J Immunol 187(6):3402-12 |
| abstractText | 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. |
