Review of Ets1 structure, function, and roles in immunity

Garrett‐Sinha, Lee Ann

doi:10.1007/s00018-012-1243-7

Cited by 166 publications

(138 citation statements)

References 139 publications

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“…In addition, Ets family proteins transcriptionally regulate CD1d1 expression in B cells [28]. Ets-1 is one of the most important transcription factors within the Ets family [29]. Ets-1 is critical in maintaining B-cell identity, and Ets-1 deficiency can drive terminal differentiation of B cells into Ig-secreting plasma cells [30].…”

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confidence: 99%

TLR9‐induced miR‐155 and Ets‐1 decrease expression of CD1d on B cells in SLE

et al. 2015

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B cells present lipid antigens to CD1d-restricted invariant natural killer T (iNKT) cells to maintain autoimmune tolerance, and this process is disrupted in systemic lupus erythematosus (SLE). Inflammation may inhibit CD1d expression to exacerbate the pathology of lupus. However, how inflammation regulates CD1d expression on B cells is unclear in SLE.In the present study, we showed that the surface expression of CD1d on B cells from SLE mice was decreased and that stimulation of inflammatory responses through TLR9 decreased the membrane and total CD1d levels of CD1d on B cells. Moreover, inflammation-related microRNA-155 (miR-155) negatively correlated with the expression of CD1d in B cells. miR-155 directly targeted the 3 -untranslated region (3 -UTR) of CD1d upon TLR9 activation in both humans and mice. The inhibitory effects of miR-155 on CD1d expression in B cells impaired their antigen-presenting capacity to iNKT cells. In addition, Ets-1, a susceptibility gene of SLE, also directly regulated the expression of the CD1d gene at the transcriptional level. These findings provide new insight into the mechanism underlying decreased CD1d expression on B cells in SLE, suggesting that inhibition of inflammation may increase CD1d expression in B cells to ameliorate SLE via modulating iNKT cells.Keywords: B cells r CD1d r Ets-1 r miR-155 r SLE Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionSystemic lupus erythematosus (SLE) is a complex and chronic autoimmune disease with an unclear etiology [1]. B cells play a central role in the pathogenesis of SLE [2], and patients with SLE exhibit abnormal B-cell activation and increased sensitivity and proliferation of B cells [3]. Moreover, the Correspondence: Dr. Yayi Hou e-mail: yayihou@nju.edu.cn clinical success of B-cell depletion therapy further proves the important role of B cells in SLE pathogenesis [4,5]. B cells not only produce antibodies and release cytokines and chemokines but also present both peptide and lipid antigens [6].CD1 family molecules are nonclassical MHC proteins related to the class I MHC proteins and are involved in the presentation of lipid antigens to T cells. Several studies have suggested that CD1d may play an immunoregulatory role in the development of lupus, and CD1d deficiency exacerbates lupus nephritis in the pristineinduced model [7] and inflammatory dermatitis in MRL-lpr/lpr C 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2015. 45: 1934-1945 Cellular immune response 1935 mice [8]. Importantly, endogenous DNA stimulates inflammatory responses through TLR9 and exacerbates lupus disease pathology [9,10]. Viral infection could downregulate the expression of CD1d in APCs, such as B cells [11,12], DCs, and macrophages [13]. A number of exogenous viruses, especially Epstein-Barr virus (EBV) [14,15], also have been linked to the pathogenesis of SLE [16]. Our previous studies have indicated that ligands for both TLR9 and TLR7 lead to B...

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TLR9‐induced miR‐155 and Ets‐1 decrease expression of CD1d on B cells in SLE

et al. 2015

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“…Intriguingly, rs4937362 locates at approximately 35 kb upstream of ETS1, which plays an important role in autoimmune diseases, such as SLE, psoriasis, RA, MS, pediatric uveitis, and hematopoietic tumors. 65,66 These findings suggest that RP11-264E20.1 rs4937362 possibility affects disease susceptibility by regulating ETS1. It is not clear why rs4937362 associated with AS þ AAU À but not in AS patients with AAU.…”

Section: Discussionmentioning

confidence: 83%

Association of Long Noncoding RNAs Polymorphisms With Ankylosing Spondylitis, Vogt-Koyanagi-Harada Disease, and Behcet's Disease

Yue

Zhang

Yang

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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“…We also found an association of radiographic severity of RA with ETS1, a highly conserved transcription factor whose expression in B cells, T cells and natural killer cells strongly affects immune cell function. Ets1 knockout mice display aberrant T cell differentiation, altered cytokine expression and increased differentiation into memory and effector T cells (65). Downregulation of Ets1 increases formation of plasma cells in part by upregulating Pax-5 and inhibiting Blimp1 activity (66).…”

Section: Discussionmentioning

confidence: 99%

Dense Genotyping of Immune-Related Regions Identifies Loci for Rheumatoid Arthritis Risk and Damage in African Americans

Danila

Laufer

Reynolds

et al. 2017

Mol Med

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More than 100 risk loci for rheumatoid arthritis (RA) have been identified in individuals of European and Asian descent, but the genetic basis for RA in African Americans is less well understood. We genotyped 610 African Americans with autoantibodypositive RA and 933 African American controls on the Immunochip (iChip) array. Using multivariable regression, we evaluated the association between iChip markers and the risk of RA and radiographic severity. The single nucleotide polymorphism (SNP) rs1964995 (odds ratio = 1.97, p = 1.28 × 10 -15 ) near HLA-DRB1 was the most strongly associated risk SNP for RA susceptibility; SNPs in AFF3, TNFSF11 and TNFSF18 loci were suggestively associated (10 -4 < p < 3.1 × 10 -6). Trans-ethnic fine mapping of AFF3 identified a 90% credible set containing previously studied variants, including rs9653442, rs7608424 and rs6712515, as well as the novel candidate variant rs11681966; several of these likely influence AFF3 gene expression level. Variants in TNFRSF9, CTLA4, IL2RA, C5/TRAF1 and ETS1 -but no variants within the major histocompatibility complex -were associated with RA radiographic severity. Conditional regression and pairwise linkage disequilibrium (LD) analyses suggest that additional pathogenic variants may be found in ETS1 and IL2RA beyond those found in other ethnicities. In summary, we used the dense genotyping of the iChip array and the unique LD structure of African Americans to validate known risk loci for RA susceptibility and radiographic severity, and to better characterize the associations of AFF3, ETS1 and IL2RA.

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Review of Ets1 structure, function, and roles in immunity

Cited by 166 publications

References 139 publications

TLR9‐induced miR‐155 and Ets‐1 decrease expression of CD1d on B cells in SLE

TLR9‐induced miR‐155 and Ets‐1 decrease expression of CD1d on B cells in SLE

Association of Long Noncoding RNAs Polymorphisms With Ankylosing Spondylitis, Vogt-Koyanagi-Harada Disease, and Behcet's Disease

Dense Genotyping of Immune-Related Regions Identifies Loci for Rheumatoid Arthritis Risk and Damage in African Americans

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