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The overexpression of Fra1 disorders the inflammatory cytokine secretion by mTEC of myasthenia gravis thymus
Author(s) -
Li Q.R.,
Ni W.P.,
Lei N.J.,
Yang J.Y.,
Xuan X.Y.,
Liu P.P.,
Gong G.M.,
Yan F.,
Feng Y.S.,
Zhao R.,
Du Y.
Publication year - 2018
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12676
Subject(s) - socs3 , myasthenia gravis , germinal center , cytokine , biology , suppressor of cytokine signalling , proinflammatory cytokine , cancer research , stat3 , immunology , microbiology and biotechnology , inflammation , signal transduction , antibody , b cell
The thymus of a myasthenia gravis (MG) patient is often accompanied by and effected with follicular hyperplasia. Inflammatory cytokines in thymus induce the formation of germinal centres (GC). MG thymic inflammatory cytokines are predominantly secreted by stromal cells. Our previous studies revealed that the expression level of the Fra1 protein, which is a Fos member of the activator protein 1 transcription factors (AP‐1), was higher in the MG thymus compared with that of the normal thymus. Based on that, we demonstrated that Fra1 was mainly expressed in medulla thymic epithelial cells (mTECs) and that the rate of Fra1 positive mTECs in the MG thymus was higher than normal. In vitro, we found that the expression of CCL‐5, CCL‐19 and CCL‐21 could be regulated by Fra1 in mTEC and that IL‐1β, IL‐6, IL‐8 and ICAM1 were downregulated in the Fra1 overexpression group and upregulated in the Fra1 knock‐down group. Meanwhile, we detected that the expression levels of suppressor of cytokine signalling 3 (SOCS3) were significantly upregulated along with the overexpression of Fra1. Hence, we considered that the overexpression of Fra1 disrupted inflammatory cytokine secretion by mTEC in the MG thymus and that STAT3 and SOCS3 were strongly involved in this process.