| First Author | Singh K | Year | 2013 |
| Journal | J Immunol | Volume | 190 |
| Issue | 6 | Pages | 2544-53 |
| PubMed ID | 23418628 | Mgi Jnum | J:193809 |
| Mgi Id | MGI:5469739 | Doi | 10.4049/jimmunol.1202399 |
| Citation | Singh K, et al. (2013) Reduced CD18 Levels Drive Regulatory T Cell Conversion into Th17 Cells in the CD18hypo PL/J Mouse Model of Psoriasis. J Immunol 190(6):2544-53 |
| abstractText | Defective development and function of CD4CD25Foxp3 regulatory T cells (Tregs) contribute to the pathogenesis of psoriasis and other autoimmune diseases. Little is known about the influence of adhesions molecules on the differentiation of Foxp3 Tregs into proinflammatory Th17 cells occurring in lesional skin and blood of psoriasis patients. In the CD18 PL/J mouse model of psoriasis, reduced expression of CD18/beta integrin to 2-16% of wild-type levels is associated with progressive loss of Tregs, impaired cell-cell contact between Tregs and dendritic cells (DCs), as well as Treg dysfunction as reported earlier. In the present investigation, Tregs derived from CD18 PL/J mice were analyzed for their propensity to differentiate into IL-17-producing Th17 cells in vivo and in in vitro Treg-DC cocultures. Adoptively transferred CD18 PL/J Tregs were more inclined toward conversion into IL-17-producing Th17 cells in vivo in an inflammatory as well as noninflammatory environment compared with CD18 PL/J Tregs. Addition of neutralizing Ab against CD18 to Treg-DC cocultures in vitro promoted conversion of CD18 PL/J Tregs to Th17 cells in a dose-dependent manner similar to conversion rates of CD18 PL/J Tregs. Reduced thymic output of naturally occurring Tregs and peripheral conversion of Tregs into Th17 cells therefore both contribute to the loss of Tregs and the psoriasiform dermatitis observed in CD18 PL/J mice. Our data overall indicate that CD18 expression levels impact Treg development as well as Treg plasticity and that differentiation of Tregs into IL-17-producing Th17 cells is distinctly facilitated by a subtotal deficiency of CD18. |
