Ask about this productRelated genes to: IKZF3 antibody
- Gene:
- IKZF3 NIH gene
- Name:
- IKAROS family zinc finger 3
- Previous symbol:
- ZNFN1A3
- Synonyms:
- Aiolos
- Chromosome:
- 17q12-q21.1
- Locus Type:
- gene with protein product
- Date approved:
- 1999-08-23
- Date modifiied:
- 2018-02-13
Related products to: IKZF3 antibody
Related articles to: IKZF3 antibody
- IKAROS, HELIOS, and AIOLOS are transcription factors predominantly expressed in hematopoietic cells, where they form heteromeric and homodimeric complexes and facilitate transcriptional regulation. IKZF proteins also associate with non-IKZF family proteins, which vary between different immune cell subtypes and their differentiation stages. Heterozygous germline loss-of-function variants in , , and cause IKAROS, HELIOS, and AIOLOS deficiencies, respectively, leading to inborn errors of immunity (IEI). Heterozygous gain-of-function (GOF) variants in result in IKAROS-GOF disease, characterized by autoimmune and allergic manifestations, whereas dominant-negative IKAROS and AIOLOS variants are associated with combined immunodeficiency. Importantly, patients with IKZF-associated IEI exhibit varying degrees of immunodeficiency, immune dysregulation, and occasional malignancies, and so, disease manifestations differ significantly among the variant types. Therefore, each variant often causes phenotypic heterogeneity, which possibly stems from diverse protein complexes formed by IKZF proteins. Besides immunoglobulin supplementation for patients with B cell defects and hematopoietic cell transplantation for severe cases, molecularly targeted therapies have been investigated for treating IKAROS-GOF disease. - Source: PubMed
Publication date: 2025/07/18
Yamashita MotoiMorio Tomohiro - T cell exhaustion has been shown to be a key resistance mechanism to efficacy of T cell engagers (TCE) in multiple myeloma (MM). Mezigdomide, a potent cereblon E3 ligase modulator that targets IKZF1 and IKZF3 simultaneously for proteasomal degradation, has been shown to modulate T cell activity in MM patients. We explored the possibility that targeting IKZF1/IKZF3 could address T cell exhaustion and restore functionality. We conducted extensive transcriptomic and epigenetic profiling on ex vivo generated exhausted T cells, using their autologous activated T cells as a comparison. Our study reveals that IKZF1 and IKZF3 are critical regulators contributing to the development and maintenance of T cell exhaustion. They regulate transcription by directly binding to promoters and enhancers, both proximal and distal, thereby altering transcriptional potential. Increased IKZF1 binding to exhaustion genes after multiple T cell stimulations results in enhancement of transcription, while binding to cytokine genes results in transcription repression. Mezigdomide treatment in exhausted T cells results in decreased expression of exhaustion-related markers, increased proinflammatory cytokine expression, and enhanced target cell killing with Alnuctamab, a B-cell maturation antigen (BCMA) targeting TCE. This study provides crucial mechanistic insights into the roles of IKZF1/IKZF3 in T cell exhaustion, supporting the rationale for combining mezigdomide with TCEs to enhance therapeutic outcomes in MM. - Source: PubMed
Publication date: 2026/05/12
Chiu HsilingZhao JunfeiBasavanhally TaraHsu Chih-ChaoAmatangelo Michael DJain GauravBjorklund Chad CHuang Ting-HsiangChen Lucia YMilne Thomas AGooding SarahParekh SamirGandhi Anita KrithivasOrtiz Estevez MariaHagner Patrick Ryan - Systemic lupus erythematosus (SLE) is a chronic, multi-organ autoimmune disease characterised by a highly heterogeneous presentation. Specific genetic variations predispose patients to the disease, and rare monogenic forms caused by single-gene variations have been identified in a small percentage of patients, often with early disease onset. In this study, we used exome sequencing in a large cohort of patient with juvenile-onset SLE to gain insight into the genetic basis of juvenile SLE (jSLE). - Source: PubMed
Publication date: 2026/04/01
Tusseau MaudKhaldi-Plassart SamiraLabalme AudreyMathieu Anne-LaureRiller QuentinMolitor CorentinSimonet ThomasViel SebastienGaboriaud ChristineThielens NicoleHeiser LionelChopin EmilieRouvet IsabelleFabien NicoleGoncalves DavidFremeaux-Bacchi VéroniqueEl-Sissy CarinePottier NicolasLarrue RomainRanchin BrunoLaurent AudreyFouillet-Desjonqueres MarineJouret MaurineMekinian ArsèneYamashita MotoiMorio TomohiroHachulla EricMelki IsabelleKone-Paut IsabelleBallot ClaireReumaux HeloisePillet PascalHarambat JeromeRichez ChristopheRicher OlivierHatchuel YvesLouillet FerielleLega Jean-ChristopheDurieu IsabelleWelfringer-Morin AnnePicard CapucineMessadi WassilaSarrot-Reynauld FrançoiseSanlaville DamienBader-Meunier BrigitteWalzer ThierryLesca GaëtanRieux-Laucat FrédéricBelot Alexandre - Immunomodulatory imide drugs (IMiDs) like lenalidomide and pomalidomide are effective in treating multiple myeloma (MM) but pose hematotoxicity risks by degrading neosubstrates Ikaros (IKZF1) and Aiolos (IKZF3). When these IMiD scaffolds are integrated into proteolysis targeting chimeras (PROTACs), they can inadvertently lead to the degradation of these neosubstrates alongside the intended protein of interest (POI), raising safety concerns. This study profiles existing PROTACs and reveals instances of undesired degradation of IMiD-associated neosubstrates. We have developed in vitro hematopoietic assays to scrutinize the IMiD effects and describe the mechanistic insights on cell differentiation rewiring towards megakaryocytes together with an activation of the interferon response that is phenocopied by an Ikaros knock-out model. Moreover, we have identified a CRBN ligand that mitigates these safety liabilities and can be effectively incorporated into PROTACs. This advancement provides a promising path toward safer preclinical development of PROTACs, especially as the field expands into chronic disease treatments beyond oncology. - Source: PubMed
Publication date: 2026/03/25
Rodrigo-Brenni Monica CKomen Jasper CHamza Ghaith MBohin NatachaAdomavicius TomasAndres AngeloBlaho StefanBörjesson UlfCollie Gavin WDe Donatis Gian MarcoEisele FrederikGao NingGohlke AndreaGrebner ChristophGustafsson FridaHock AndreasKankkonen CeciliaKumar PraveenLeonard EmilyanneLi XinMacdonald RuthMadeyski-Bengtson KatjaMiele EricNevin PhilipOverman JeroenPachl FionaPathe ClaudioPerry Matthew W DPhillips ChristopherPike AndyPurvis IanRasmusson TimothyRegan SophieReilly LindaRose JonathanStorer R IanWang JingwenZhai XiangMichaelides Iacovos NMoreau Kevin - The pathophysiology of multiple sclerosis (MS) bears notable similarities to the dysregulated inflammatory response occurring during coronavirus disease 2019 (COVID-19) infection. B cells play a pivotal role among immune cells in the pathogenesis of both these diseases. Consequently, clarifying the molecular mechanism underlying B cell function in COVID-19 and MS is of great significance for formulating more efficient treatment strategies. A comprehensive analysis integrating single-cell RNA sequencing (scRNA-seq), genome-wide association study, and expression quantitative trait locus data from patients with COVID-19 and MS was performed. Gene set enrichment analysis revealed pathways and functional roles associated with the key genes, while pseudotime analysis tracked their expression patterns across different B cell developmental trajectories. The results of scRNA-seq analysis showed that, in comparison with the healthy control group, the proportion of B cells rose in patients with COVID-19 and those with MS. Through differential expression analysis and Mendelian randomization analysis, , , and were identified as risk factors for both COVID-19 and MS, whereas was characterized as a protective factor against these two conditions. The findings of the pseudotime analysis indicated that only had differential expression across different branches of B cells. 's role in promoting immune inflammation and inhibiting metabolism could potentially be linked to the onset and comorbidity of COVID-19 and MS. This emphasizes not only the possible interaction mechanisms between these two diseases but also their clinical significance. - Source: PubMed
Publication date: 2026/03/17
Chen ShupingRuan JunCheng SikaiZheng HuifangChang TianyuBao GuichunZhu ZijingLi XinglinZhao WeiZheng Kunwen