Oestrogen up-regulates interleukin-21 production by CD4(+) T lymphocytes in patients with systemic lupus erythematosus.
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 CD4(+) T cells were higher in SLE patients than in healthy controls. Exposure of CD4(+) T cells from SLE patients to 17β-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 CD4(+) 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 CD4(+) T cells via MAPK-dependent pathways in SLE patients, which in turn induces increased antibody production by B cells.
The Rheumatism Research Centre, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seocho-gu, Seoul, South Korea; Division of Rheumatology, Department of Internal Medicine, Centre for Rheumatic Disease, Seoul St Mary's Hospital, The Catholic University of Korea, Seocho-gu, Seoul, South Korea.
Jennifer
J
Lee
Eun-Kyoung
EK
Shin
Seon-Yeong
SY
Lee
Yang-Mi
YM
Her
Mi-Kyung
MK
Park
Seung-Ki
SK
Kwok
Ji Hyeon
JH
Ju
Kyung-Su
KS
Park
Ho-Youn
HY
Kim
Mi-La
ML
Cho
Sung-Hwan
SH
Park
D000328:Adult; D000917:Antibody Formation / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000276:immunology / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000276:immunology; D008875:Middle Aged; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000098546:Interleukin-21
D004967:Estrogens; D007378:Interleukins; D004958:Estradiol; D048049:Extracellular Signal-Regulated MAP Kinases; D000098546:Interleukin-21
autoantibody; interleukin-21; mitogen-activated protein kinase; oestrogen; systemic lupus erythematosus