Early Growth Response Gene 1 Benefits Autoimmune Disease by Promoting Regulatory T Cell Differentiation as a Regulator of Foxp3, 2025, Yang et al

[Wyva]

Abstract​

Foxp3+ regulatory T (Treg) cells, as one of the subtypes of CD4+ T cells, are the crucial gatekeeper in the pathogenesis of self-antigen reactive diseases. In this context, we demonstrated that the selective ablation of early growth response gene 1 (Egr-1) in CD4+ T cells exacerbated experimental autoimmune encephalomyelitis (EAE) in murine models. The absence of Egr-1 in CD4+ T cells, obtained from EAE mice and naïve CD4+ T cells, impeded the differentiation and influence of Treg. Importantly, in CD4+ T cells of multiple sclerosis patients, both Egr-1 and Foxp3 were found to decrease. Further studies showed that distinct from the classical Smad3 route, TGF-β could activate Egr-1 through the Raf–Erk signaling route to promote Foxp3 genetic modulation, thereby promoting Treg cell differentiation and reducing EAE inflammation. A novel natural Egr-1 agonist, calycosin, was found to attenuate EAE progression by regulating the differentiation of Treg. Together, the above results indicate the value of Egr-1, as a novel Foxp3 transactivator, for the differentiation of Treg cells in the development of self-antigen reactive diseases.

Open access: https://spj.science.org/doi/10.34133/research.0662

 

[Wyva]

Paper suggested by @Utsikt

 

[Utsikt]

Thank you @Wyva

FOXP3 has popped up in a few ME/CFS papers, so I thought it would be good to add this to the record.

 

[Jonathan Edwards]

Foxp3+ regulatory T (Treg) cells, as one of the subtypes of CD4+ T cells, are the crucial gatekeeper in the pathogenesis of self-antigen reactive diseases

On what evidence? Almost certainly wrong.

In this context, we demonstrated that the selective ablation of early growth response gene 1 (Egr-1) in CD4+ T cells exacerbated experimental autoimmune encephalomyelitis (EAE) in murine models.

The old yak dung effect? Almost anything makes EAE better or worse and it has nothing to do with human MS.


There is no reason to think that any of this has any relevance to human autoimmunity, where self T cell responses are almost never found. But people do not learn.