The overexpression of Fra1 disorders the inflammatory cytokine secretion by mTEC of myasthenia gravis thymus

Abstract

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.

Interactome Networks of FOSL1 and FOSL2 in Human Th17 Cells

“…It is established that PPI networks of TFs are significantly altered in cases of mutations or disease . Because FOS-like proteins have important implications in the development of autoimmune disorders, − their interactomes could serve as a crucial resource in the field of disease biology. Studying the changes in their PPIs under adverse physiological conditions could help predict diagnostic markers and therapeutic targets for Th17-associated pathologies.…”

The roles of SOCS3 and STAT3 in bacterial infection and inflammatory diseases

“…In summary, the phenotypes from previous studies generated by enforcing or preventing stat3 ‐mediated signalling in TECs reveal that STAT3 activation plays a key role in TECs maintenance and T cell development in the thymus, but this needs more precise studies . Li et al found out that inflammatory cytokines such as IL‐6, IL‐8 and ICAM1 could be downregulated by Fra1 in medulla thymic epithelial cell line, and STAT3 and SOCS3 were highly upregulated along with protein in the thymus of myasthenia gravis patient, which demonstrated that those two proteins are strongly involved in the process of disruption inflammatory cytokine secretion …”

Mapping Interactome Networks of FOSL1 and FOSL2 in Human Th17 Cells

“…It is established that PPI networks of TFs are significantly altered in cases of mutations or disease 95 . Since FOS-like proteins have important implications in the development of autoimmune disorders [96][97][98][99][100] , their interactomes could serve as a crucial resource in the field of disease-biology. Studying the changes in their protein-protein interactions under adverse physiological conditions, could help predict diagnostic markers and therapeutic targets for Th17-associated pathologies.…”