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Oestrogen up‐regulates interleukin‐21 production by CD 4 + T lymphocytes in patients with systemic lupus erythematosus
Author(s) -
Lee Jennifer,
Shin EunKyoung,
Lee SeonYeong,
Her YangMi,
Park MiKyung,
Kwok SeungKi,
Ju Ji Hyeon,
Park KyungSu,
Kim HoYoun,
Cho MiLa,
Park SungHwan
Publication year - 2014
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/imm.12263
Subject(s) - peripheral blood mononuclear cell , autoantibody , immune system , antibody , endocrinology , medicine , immunology , lupus erythematosus , pathogenesis , systemic lupus erythematosus , autoimmune disease , biology , disease , in vitro , biochemistry
Summary Systemic lupus erythematosus ( SLE ) is an autoimmune disease in which abnormal immune responses are mediated by tissue‐binding autoantibodies and immune complex deposition. Because most SLE patients are women of child‐bearing age, oestrogen has been suggested to play an important role in SLE pathogenesis. One proposed role is to induce B ‐cell activation, culminating in increased autoantibody production. Interleukin‐21 ( IL ‐21) has been shown to be crucial in the differentiation of activated B cells into plasma cells. We therefore hypothesized that oestrogen up‐regulates IL ‐21 production and induces subsequent B ‐cell activation in SLE patients. Peripheral blood was obtained from 22 SLE patients and 16 healthy controls. Expression levels of IL ‐21 and its receptor in serum, peripheral blood mononuclear cells, and CD 4 + T cells were higher in SLE patients than in healthy controls. Exposure of CD 4 + T cells from SLE patients to 17 β ‐oestradiol led to a dose‐ and time‐dependent increase in IL ‐21 expression, which was abolished in the presence of mitogen‐activated protein kinase ( MAPK ) ( MAPK kinase, p38, Jun N‐terminal kinase) inhibitors. B cells from healthy controls showed increased antibody production when they were co‐cultured with oestrogen‐treated CD 4 + T cells from SLE patients. Treatment with IL ‐21 antibody abrogated the increased antibody production of the co‐culture systems. This study revealed the association between oestrogen and IL ‐21 in SLE patients. Oestrogen up‐regulates IL ‐21 expression of CD 4 + T cells via MAPK ‐dependent pathways in SLE patients, which in turn induces increased antibody production by B cells.