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Oestrogen modulates experimental autoimmune encephalomyelitis and interleukin‐17 production via programmed death 1
Author(s) -
Wang Chunhe,
Dehghani Babak,
Li Yuexin,
Kaler Laurie J.,
Vandenbark Arthur A.,
Offner Halina
Publication year - 2009
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2008.03051.x
Subject(s) - experimental autoimmune encephalomyelitis , downregulation and upregulation , foxp3 , immunology , encephalomyelitis , multiple sclerosis , immune system , regulator , biology , medicine , gene , biochemistry
Summary The mechanism by which oestrogens suppress experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, is only partially understood. We here demonstrate that treatment with 17β‐oestradiol (E 2 ) in C57BL/6 mice boosted the expression of programmed death 1 (PD‐1), a negative regulator of immune responses, in the CD4 + FoxP3 + regulatory T (Treg) cell compartment in a dose‐dependent manner that correlated with the efficiency of EAE protection. Administration of E 2 at pregnancy levels but not lower concentrations also enhanced the frequency of Treg cells. Additionally, E 2 treatment drastically reduced the production of interleukin‐17 (IL‐17) in the periphery of immunized mice. However, E 2 treatment did not protect against EAE or suppress IL‐17 production in PD‐1 gene‐deficient mice. Finally, E 2 failed to prevent Treg‐deficient mice from developing spontaneous EAE. Taken together, our results suggest that E 2 ‐induced protection against EAE is mediated by upregulation of PD‐1 expression within the Treg‐cell compartment.