Heterozygous Variants in the DNA-binding Domain of c-Myb May Affect Normal B/T Cell Development

Smits, Bas M.; Hartley, Taila; Dünnebach, Ester; Bartels, Marije; Boycott, Kim; Kernohan, Kirstin D.; Dyment, David A.; Giltay, Jacques C.; Haddad, Elie; Jarinova, Olga; Montfrans, Joris van; Royen‐Kerkhof, Annet van; Veken, Lars T. van der; Witte, Moniek de; Nierkens, Stefan; Pham‐Huy, Anne; Leavis, Helen L.

doi:10.1097/hs9.0000000000000774

Cited by 2 publications

(1 citation statement)

References 16 publications

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“…Among these monoallelic variants, missense variants in the genes encoding transcriptional regulators have received attention. For instance, variants of STAT1, c-MYB, and BCL11B, have been isolated from human patients with IEI (3)(4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

Impaired tissue homing by the Ikzf3N159S variant is mediated by interfering with Ikaros function

Chang,

Yamashita,

Padhi

et al. 2023

Front. Immunol.

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AIOLOS, encoded by IKZF3, is a member of the IKZF family of proteins that plays an important role in regulating late B-cell differentiation. Human individuals heterozygous for the AIOLOS p.N160S variant displayed impaired humoral immune responses as well as impaired B and T cell development. We have previously reported that a mouse strain harboring an Ikzf3N159S allele that corresponds to human IKZF3N160S recapitulated immune-deficient phenotypes, such as impaired B cell development and loss of CD23 expression. In this study, we investigated the effect of the Ikzf3N159S variant and found that B1a cell development was impaired in Ikzf3N159S/N159S mice. In addition, CD62L expression was severely decreased in both B and T lymphocytes by the Ikzf3N159S mutation, in a dose-dependent manner. Mixed bone marrow chimera experiments have revealed that most immunodeficient phenotypes, including low CD62L expression, occur in intrinsic cells. Interestingly, while Ikzf3N159S/N159S lymphocytes were still present in the spleen, they were completely outcompeted by control cells in the lymph nodes, suggesting that the capacity for homing or retention in the lymph nodes was lost due to the Ikzf3N159S mutation. The homing assay confirmed severely decreased homing abilities to lymph nodes of Ikzf3N159S/N159S B and T lymphocytes but selective enrichment of CD62L expressing Ikzf3N159S/N159S lymphocytes in lymph nodes. This finding suggests that impaired CD62L expression is the major reason for the impaired homing capacity caused by the Ikzf3N159S mutation. Interestingly, an excess amount of Ikaros, but not Aiolos, restored CD62L expression in Ikzf3N159S/N159S B cells. Together with the loss of CD62L expression due to Ikaros deficiency, the AiolosN159S mutant protein likely interferes with Ikaros function through heterodimerization, at least in activating the Sell gene encoding CD62L expression. Thus, our results revealed that AiolosN159S causes some immunodeficient phenotypes via the pathogenesis referred to as the heterodimeric interference as observed for AiolosG158R variant.

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Section: Introductionmentioning

confidence: 99%

Impaired tissue homing by the Ikzf3N159S variant is mediated by interfering with Ikaros function

Chang,

Yamashita,

Padhi

et al. 2023

Front. Immunol.

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A Literature Review and Meta-Analysis on the Potential Use of miR-150 as a Novel Biomarker in the Detection and Progression of Multiple Sclerosis

Arcas,

Fratila,

Moga

et al. 2024

JPM

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Background: MicroRNA-150 (miR-150) plays a critical role in immune regulation and has been implicated in autoimmune diseases like Multiple Sclerosis (MS). This review aims to evaluate miR-150’s potential as a biomarker for MS, necessitating this review to consolidate current evidence and highlight miR-150’s utility in improving diagnostic accuracy and monitoring disease progression. Methods: A comprehensive literature search was conducted in databases like PubMed, Scopus, Google Scholar, SciSpace, MDPI and Web of Science, adhering to PRISMA guidelines. Studies focusing on miR-150 implications in MS were included. Data extraction was conducted, while quality assessment was done using the NOS and AMSTAR 2 tools. With the extracted data a statistical analyses conducted. Results: 10 eligible articles were included in review. Findings show that miR-150 levels were consistently deregulated in MS patients compared to healthy controls, correlating with disease severity and clinical parameters such as (EDSS) scores and disease activity. Additionally, miR-150 is implicated in the inflammatory pathogenesis of MS, affecting immune cell regulation and inflammatory pathways. Conclusions: MiR-150 is a promising biomarker for MS, showing significant potential for improving diagnostic accuracy and monitoring disease progression. Its consistent deregulation in MS patients and correlation with clinical parameters underscore its clinical utility. Further research should validate miR-150’s salivary presence and its possible usage as a novel biomarker and therapeutic potential in the development of MS.

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Heterozygous Variants in the DNA-binding Domain of c-Myb May Affect Normal B/T Cell Development

Cited by 2 publications

References 16 publications

Impaired tissue homing by the Ikzf3N159S variant is mediated by interfering with Ikaros function

Impaired tissue homing by the Ikzf3N159S variant is mediated by interfering with Ikaros function

A Literature Review and Meta-Analysis on the Potential Use of miR-150 as a Novel Biomarker in the Detection and Progression of Multiple Sclerosis

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