| First Author | Subramanian S | Year | 2011 |
| Journal | Immunology | Volume | 132 |
| Issue | 3 | Pages | 340-7 |
| PubMed ID | 21091909 | Mgi Jnum | J:168493 |
| Mgi Id | MGI:4888450 | Doi | 10.1111/j.1365-2567.2010.03380.x |
| Citation | Subramanian S, et al. (2011) Oestrogen-mediated protection of experimental autoimmune encephalomyelitis in the absence of Foxp3+ regulatory T cells implicates compensatory pathways including regulatory B cells. Immunology 132(3):340-7 |
| abstractText | Oestrogen (17beta-oestradiol, E(2) ) is a highly effective treatment for experimental autoimmune encephalomyelitis (EAE) that may potentiate Foxp3(+) regulatory T (Treg) cells, which in turn limit the expansion of encephalitogenic T-cell specificities. To determine if Treg cells constitute the major non-redundant protective pathway for E(2) , we evaluated E(2) protection of EAE after targeted deletion of Foxp3 expression in Foxp3-DTR mice. Unexpectedly, E(2) -treated Foxp3-deficient mice were completely protected against clinical and histological myelin oligodendrocyte glycoprotein (MOG)-35-55 peptide-induced EAE before succumbing to diphtheria toxin-induced mortality. This finding indicated the presence of alternative E(2) -dependent EAE-protective pathways that could compensate for the lack of Treg cells. Further investigation revealed that E(2) treatment inhibited proliferation and expression of CCL2 and CXCL2, but enhanced secretion of interleukin-10 (IL-10) and IL-13 by MOG-35-55-specific spleen cells. These changes occurred concomitantly with increased expression of several chemokines and receptors, including CXCL13 and CXCR5, and the negative co-activation molecules, PD-L1 and B7.2, by B cells and dendritic cells. Furthermore, E(2) treatment resulted in higher percentages of spleen and lymph node T cells expressing IL-17, interferon-gamma and tumour necrosis factor-alpha, but with lower expression of CCR6, suggesting sequestration of MOG-35-55 peptide-specific T cells in peripheral immune organs. Taken together, these data suggest that E(2) -induced mechanisms that provide protection against EAE in the absence of Foxp3(+) Treg cells include induction of regulatory B cells and peripheral sequestration of encephalitogenic T cells. |
