IKZF4

Last update 23 Jan 2025

Basic Info

Synonyms

Eos, IKAROS family zinc finger 4, Ikaros family zinc finger protein 4

+ [4]

Introduction

DNA-binding protein that binds to the 5'GGGAATRCC-3' Ikaros-binding sequence. Transcriptional repressor. Interacts with SPI1 and MITF to repress transcription of the CTSK and ACP5 promoters via recruitment of corepressors SIN3A and CTBP2. May be involved in the development of central and peripheral nervous systems. Essential for the inhibitory function of regulatory T-cells (Treg). Mediates FOXP3-mediated gene silencing in regulatory T-cells (Treg) via recruitment of corepressor CTBP1 (By similarity).

100 Clinical Results associated with IKZF4

100 Translational Medicine associated with IKZF4

0 Patents (Medical) associated with IKZF4

Literatures (Medical) associated with IKZF4

01 Dec 2024·Journal of Autoimmunity

High-content multimodal analysis supports the IL-7/IL-7 receptor axis as a relevant therapeutic target in primary Sjögren's syndrome

Article

Author: Pers, Jacques-Olivier ; Chatzis, Loukas ; Laigle, Laurence ; Devauchelle-Pensec, Valérie ; Moingeon, Philippe ; Bretin, Sylvie ; Elouej, Sahar ; Le Dantec, Christelle ; Duguet, Fanny ; Soret, Perrine ; Poirier, Nicolas ; Cornec, Divi ; Hemon, Patrice ; Desvaux, Emiko

OBJECTIVEWhile the involvement of IL-7/IL-7R axis in pSS has been described in relation to T cells, little is known about the contribution of this pathway in relationship with other immune cells, and its implication in autoimmunity. Using high-content multiomics data, we aimed at characterizing IL-7R expressing cells and the involvement of IL-7/IL-7R pathway in pSS pathophysiology.METHODSAn IL-7 signature established using RNA-sequencing of human PBMCs incubated with IL-7 was applied to 304 pSS patients, and on RNA-Seq datasets from tissue biopsies. High-content immunophenotyping using flow and imaging mass cytometry was developed to characterize peripheral and in situ IL-7R expression.RESULTSWe identified a blood 4-gene IL-7 module (IKZF4, KIAA0040, PGAP1 and SOS1) associated with anti-SSA/Ro positiveness in patients as well as disease activity, and a tissue 5-gene IL-7 module (IL7R, PCED1B, TNFSF8, ADAM19, MYBL1) associated with infiltration severity. We confirmed expression of IL-7R on T cells subsets, and further observed upregulation of IL-7R on double-negative (DN) B cells, and especially DN2 B cells. IL-7R expression was increased in pSS compared to sicca patients with variations seen according to the degree of infiltration. When expressed, IL-7R was mainly found on epithelial cells, CD4⁺ and CD8⁺ T cells, switched memory B cells, DN B cells and M1 macrophages.CONCLUSIONThis exhaustive characterization of the IL-7/IL-7R pathway in pSS pathophysiology established that two IL-7 gene modules discriminate pSS patients with a high IL-7 axis involvement. Their use could guide the implementation of an anti-IL-7R targeted therapy in a precision medicine approach.

01 Oct 2024·Alternative therapies in health and medicine

Association analysis of the IKZF4 gene with Alopecia Areata in the Chinese Han population.

Article

Author: Sheng, Youyu ; Miao, Ying ; Qi, Sisi ; Yang, Qinping ; Hu, Ruiming

ObjectiveThe IKZF4(Ikaros family zinc finger 4) gene encodes Eos, a zinc finger transcription factor that belongs to the Ikaros family. High expression of Eos on Treg cells is important for the suppression of autoimmune responses and immune homeostasis. It has been suggested that the SNP in IKZF4 may influence the pathogenesis of AA(alopecia areata). The purpose of this study was to explore the relationship between IKZF4 polymorphism and AA in the Chinese Han population.MethodsWe examined 459 patients and 434 controls in this study. The rs1701704 polymorphism was evaluated using HRM analysis and direct sequencing.ResultsThe prevalence of the C/C, A/C, and A/A genotypes in AA patients was 7.4%, 37.5% and 55.1%, respectively. There were significant differences in genotype distribution and allele frequencies between AA and the control group (P < .0001). The frequency of the C allele in the AA group was significantly higher (P < .0001), and the frequencies of the C allele and C/C genotype in patients with family history were higher (P < .0001; P = .001).ConclusionsThe rs1701704 SNP of IKZF4 may be a genetic marker for assessing the risk of AA in the Chinese Han population.

18 May 2024·Human Molecular Genetics

A multi-ancestry genome-wide association study in type 1 diabetes

Article

Author: Robertson, Catherine C ; Onengut-Gumuscu, Suna ; Farber, Emily ; Tern, Courtney ; Campolieto, Paul ; Rich, Stephen S ; Zhou, Wei ; Michalek, Dominika A ; Chen, Wei-Min

AbstractType 1 diabetes (T1D) is an autoimmune disease caused by destruction of the pancreatic β-cells. Genome-wide association (GWAS) and fine mapping studies have been conducted mainly in European ancestry (EUR) populations. We performed a multi-ancestry GWAS to identify SNPs and HLA alleles associated with T1D risk and age at onset. EUR families (N = 3223), and unrelated individuals of African (AFR, N = 891) and admixed (Hispanic/Latino) ancestry (AMR, N = 308) were genotyped using the Illumina HumanCoreExome BeadArray, with imputation to the TOPMed reference panel. The Multi-Ethnic HLA reference panel was utilized to impute HLA alleles and amino acid residues. Logistic mixed models (T1D risk) and frailty models (age at onset) were used for analysis. In GWAS meta-analysis, seven loci were associated with T1D risk at genome-wide significance: PTPN22, HLA-DQA1, IL2RA, RNLS, INS, IKZF4-RPS26-ERBB3, and SH2B3, with four associated with T1D age at onset (PTPN22, HLA-DQB1, INS, and ERBB3). AFR and AMR meta-analysis revealed NRP1 as associated with T1D risk and age at onset, although NRP1 variants were not associated in EUR ancestry. In contrast, the PTPN22 variant was significantly associated with risk only in EUR ancestry. HLA alleles and haplotypes most significantly associated with T1D risk in AFR and AMR ancestry differed from that seen in EUR ancestry; in addition, the HLA-DRB1*08:02-DQA1*04:01-DQB1*04:02 haplotype was ‘protective’ in AMR while HLA-DRB1*08:01-DQA1*04:01-DQB1*04:02 haplotype was ‘risk’ in EUR ancestry, differing only at HLA-DRB1*08. These results suggest that much larger sample sizes in non-EUR populations are required to capture novel loci associated with T1D risk.

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IKZF4

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