ETS-1 facilitates Th1 cell-mediated mucosal inflammation in inflammatory bowel diseases through upregulating CIRBP

He, Qiong; Gao, Han; Chang, Yunli; Wu, Xiaohan; Lin, Ritian; Li, Gengfeng; Lin, Jian; Lü, Huafei; Chen, Huimin; Li, Zhitao; Cong, Yingzi; Yao, Jun; Liu, Zhanju

doi:10.1016/j.jaut.2022.102872

Cited by 16 publications

(13 citation statements)

References 49 publications

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“…Furthermore, cigarette smoke is known to alter the expression of ETS1 [ 44 ]. ETS1 has also been linked to CD, as it is highly expressed in CD4+ T-cells from patients with inflammatory bowel disease and promotes Th1-driven mucosal inflammation through cold-inducible RNA binding protein (CIRBP) [ 45 ]. These changes would likely contribute to worse CD outcomes.…”

Section: Discussionmentioning

confidence: 99%

Smoking Suppresses the Therapeutic Potential of Adipose Stem Cells in Crohn’s Disease Patients through Epigenetic Changes

Boronat-Toscano

Vañó

Monfort-Ferré

et al. 2023

Cells

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Patients with Crohn’s disease (CD) who smoke are known to have a worse prognosis than never-smokers and a higher risk for post-surgical recurrence, whereas patients who quit smoking after surgery have significantly lower post-operative recurrence. The hypothesis was that smoking induces epigenetic changes that impair the capacity of adipose stem cells (ASCs) to suppress the immune system. It was also questioned whether this impairment remains in ex-smokers with CD. ASCs were isolated from non-smokers, smokers and ex-smokers with CD and their interactions with immune cells were studied. The ASCs from both smokers and ex-smokers promoted macrophage polarization to an M1 pro-inflammatory phenotype, were not able to inhibit T- and B-cell proliferation in vitro and enhanced the gene and protein expression of inflammatory markers including interleukin-1b. Genome-wide epigenetic analysis using two different bioinformatic approaches revealed significant changes in the methylation patterns of genes that are critical for wound healing, immune and metabolic response and p53-mediated DNA damage response in ASCs from smokers and ex-smokers with CD. In conclusion, cigarette smoking induces a pro-inflammatory epigenetic signature in ASCs that likely compromises their therapeutic potential.

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Section: Discussionmentioning

confidence: 99%

Smoking Suppresses the Therapeutic Potential of Adipose Stem Cells in Crohn’s Disease Patients through Epigenetic Changes

Boronat-Toscano

Vañó

Monfort-Ferré

et al. 2023

Cells

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“…Bone marrow chimeras confirmed that expression of the transgenic Ets1 in bone-marrow-derived cells was required for the phenotype. The cold-inducible RNA-binding protein (CIRBP) was identified as a gene regulated by Ets1 which is involved in Th1 cell-driven immune responses in IBD (He et al, 2022). The super-enhancer described above that is located downstream of the Ets1 gene is needed for differentiation of Th1 cells (Chandra et al, 2023).…”

Section: Autoimmune and Inflammatory Phenotypes In Ets1 Knockout Micementioning

confidence: 99%

“…Another study comparing gene expression patterns in two bowel locations (ileum and colon) and in three disease states (control, CD, or UC), also found Ets1 to be downregulated in CD as compared to control samples (Hughes, 2005). However, two more recent studies have found Ets1 to be upregulated in both CD and UC and its levels were highest in the inflamed regions of the gut as compared to less affected areas and positively correlated with disease severity (Ge et al, 2019; He et al, 2022). This is consistent with the high expression of Ets1 in lymphocytes, which are enriched at sites of inflammation.…”

Section: Inflammatory Bowel Diseasementioning

confidence: 99%

“…This is consistent with the high expression of Ets1 in lymphocytes, which are enriched at sites of inflammation. Ets1 mRNA was also found to be elevated in the peripheral blood T cells of UC and CD patients as compared to healthy donors (He et al, 2022). The relevance of this finding is unclear, since Ets1 is typically reduced in T cells upon their activation.…”

Section: Inflammatory Bowel Diseasementioning

confidence: 99%

“…Treatment of healthy donor CD4 T cells with IL‐1β or TNF‐α increases Ets1 mRNA levels (He et al, 2022). In contrast, IBD patients that respond clinically to the anti‐TNF‐α drug infliximab (IFX) show a reduced expression of Ets1 mRNA in CD4 T cells after the same treatment.…”

Section: Inflammatory Bowel Diseasementioning

confidence: 99%

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An update on the roles of transcription factor Ets1 in autoimmune diseases

Garrett‐Sinha

2023

WIREs Mechanisms of Disease

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Transcription factors are crucial to regulate gene expression in immune cells and in other cell types. In lymphocytes, there are a large number of different transcription factors that are known to contribute to cell differentiation and the balance between quiescence and activation. One such transcription factor is E26 oncogene homolog 1 (Ets1). Ets1 expression is high in quiescent B and T lymphocytes and its levels are decreased upon activation. The human ETS1 gene has been identified as a susceptibility locus for many autoimmune and inflammatory diseases. In accord with this, gene knockout of Ets1 in mice leads to development of a lupus‐like autoimmune disease, with enhanced activation and differentiation of both B cells and T cells. Prior reviews have summarized functional roles for Ets1 based on studies of Ets1 knockout mice. In recent years, numerous additional studies have been published that further validate ETS1 as a susceptibility locus for human diseases where immune dysregulation plays a causative role. In this update, new information that further links Ets1 to human autoimmune diseases is organized and collated to serve as a resource. This update also describes recent studies that seek to understand molecularly how Ets1 regulates immune cell activation, either using human cells and tissues or mouse models. This resource is expected to be useful to investigators seeking to understand how Ets1 may regulate the human immune response, particularly in terms of its roles in autoimmunity and inflammation.This article is categorized under: Immune System Diseases > Genetics/Genomics/Epigenetics Immune System Diseases > Molecular and Cellular Physiology

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Regulation of cold-inducible RNA-binding protein (CIRBP) in response to cellular stresses

Corre

Lebreton

2024

Biochimie

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ETS-1 facilitates Th1 cell-mediated mucosal inflammation in inflammatory bowel diseases through upregulating CIRBP

Cited by 16 publications

References 49 publications

Smoking Suppresses the Therapeutic Potential of Adipose Stem Cells in Crohn’s Disease Patients through Epigenetic Changes

Smoking Suppresses the Therapeutic Potential of Adipose Stem Cells in Crohn’s Disease Patients through Epigenetic Changes

An update on the roles of transcription factor Ets1 in autoimmune diseases

Regulation of cold-inducible RNA-binding protein (CIRBP) in response to cellular stresses

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