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Gene & Protein in Disease The roles and mechanisms of ETS1 in diseases

and Th17 cells are directly linked to the occurrence and and multivariate studies, researchers found that ETS1
development of SLE has been gaining traction, but the rs73013527 has an indirect impact on serum receptor
specific mechanism involved has yet to be determined [18-23] . activator of nuclear factor kappa B ligand (RANKL) levels
in RA patients . A recent study also established ETS1
[28]
Moreover, a recent article by Kim et al. suggested
that ETS1 inhibits T follicular helper Type 2 (Tfh2) cells, as a crucial transcription factor by virtue of its ability to
thereby preventing the onset of SLE . Specifically, a promote the production of RANKL and tissue-destructing
[24]
[29]
decrease in ETS1 expression in CD4 T cells in SLE patients fibroblasts . In addition, ETS1 may affect serum RANKL
+
leads to an increase in the secretion of IL-4 by GATA- levels through the cytokine network, especially given that
[28]
3 Bcl6 Tfh2 cells, thereby increasing the production RA patients have markedly increased IL-17 levels .
+
+
of the autoantibodies IgE and IgG1 . Kim et al. also 3.3. Autoimmune thyroiditis (AIT)
[24]
demonstrated that SLE autoimmunity was caused by the
deletion of ETS1 specifically in CD4 T cells, rather than AIT is a disease in which lymphocytes infiltrate the
+
in B cells or dendritic cells (DCs), and was linked to the impaired thyroid through antibodies. Recent studies have
spontaneous expansion of Tfh2 cells . This research shown that high miR-326 expression is associated with
[24]
provides evidence that ETS1 regulates CD4 T-cell a significant increase of Th17 cells and decreased ETS1
+
differentiation in the pathogenesis of SLE. protein levels for Th17 differentiation during the onset
and development of AIT [30,31] . miR-326 may target the Ets1
It has been shown that lacking ETS1 leads to more protein to trigger iodide-induced AIT since the expression
intrinsic changes in B cells, including an expansion of the of Ets1 in AIT mice is adversely linked with miR-326
B cell population in the marginal zone, increased antibody levels . A subsequent study further verified that miR-326
[30]
secretion in plasma cells, an increased B-cell proportion levels lead to AIT by controlling the Th17/Treg balance
with a memory phenotype, and an increased autoantibody through ETS1 .
[31]
[25]
titer . Moreover, these changes are not accompanied by
significant T-cell over activation. However, changes in 3.4. Multiple sclerosis (MS)
biological processes that are regulated by ETS1, including MS, an autoimmune disease, is a persistent neurological
the development of antibody-secreting cells and memory condition that primarily impacts the central nervous
B cells and the production of autoantibodies, are not system, encompassing both the brain and the spinal cord.
obvious in B-cell ETS1-knockout mice compared with Li et al. reported that the upregulation of miR-1-3p in
those in mice with complete ETS1 knockout . A recent patients with recurrent MS and Th17 cells, as well as miR-
[25]
study revealed that ETS1 downregulation could increase 1-3p expression, was strongly linked with the severity of
miR-326 expression in B cells of SLE patients, thereby MS. In the peripheral blood mononuclear cells of relapsed
driving the growth of plasmablasts and the generation of patients with recurrent MS, the expression of ETS1 (a target
antibodies . Although the mechanism through which gene of miR-1-3p) was reduced, while the upregulation of
[26]
ETS1 participates in SLE still lacks clarity, it is obvious ETS1 inhibited the expression of inflammation-related
that B cells play an important role in this regard. This is genes (CXCL3, CSF2, and IL-23R), thereby decreasing the
evidenced by the role of abnormal interactions between pathogenicity of Th17 cells . The overexpression of miR-
[32]
T cells and B cells induced by ETS1 knockdown in the 1-3p in naïve CD4 T cells has a positive effect on Th17
+
mechanism underlying SLE pathogenesis, although SLE- cell differentiation and is positively correlated with the
like symptoms are manifested in patients with a lack of progression of MS. Targeting miR-1-3p with ETS1 could
ETS1 in T cells, rather than in B cells . reduce the level of miR-1-3p and inhibit the pathogenic
[24]
response of Th17 cells . Dysfunction of the blood-brain
[32]
3.2. Rheumatoid arthritis (RA) barrier (BBB) has been recognized as a contributor to MS,
RA is a complex autoimmune disease that primarily affects and disturbances in vascular stability and barrier function
joints. In RA, the immune system attacks the host joint are caused by the endothelial-to-mesenchymal transition
tissues, causing pain and swelling, and impairing joint (EndMT), a mechanism linked to endothelial dysfunction.
function. However, the pathogenesis of RA is yet unknown. The effect of EndMT in MS is still unclear, but recently,
It has been found that the single nucleotide polymorphism a study found that ETS1 serves as the primary regulator
rs73013527 of ETS1 was significantly positively correlated of EndMT, which is connected to diminished barrier
with RA-sensitive DAS28 and C-reactive protein in the integrity , providing compelling evidence on the pivotal
[33]
Han Chinese population . At present, studies on the functional role of EndMT in the disruption of the blood-
[27]
function and mechanism of ETS1 in the pathogenesis of brain barrier, which is a critical feature in MS pathogenesis.
RA are scarce. However, through a series of univariate Moreover, the authors proposed that ETS1 might serve as

Volume 2 Issue 4 (2023) 3 https://doi.org/10.36922/gpd.2141