Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 19, 2024

dominated by infections, while others manifest primarily with variable form of immune dysregulation. In this complex scenario, disorders presenting a phenotype caused loss tolerance leading to autoimmunity, autoinflammation, lymphoproliferation, and/or severe atopy have come be recognized as Primary Immune Regulatory Disorders (PIRDs). They encompass distinct set secondary failure in different regulatory pathways; hence, enables subgrouping into categories. 2018, the term Tregopathies was first introduced: it refers group IEI which affected target cells are T (Treg). This initially included mutations FOXP3, CD25, CTLA-4, LRBA, BACH2, IL10, and gain function (GOF) STAT3. Since then, IUIS expert committee has added new genes category, including FERMT1, CD122, DEF6, IKAROS GOF (2,3). Research Topic, Kennedy-Batalla colleagues provide comprehensive overview Treg focusing on: i) advances controversies evaluation Tregs; ii) current knowledge gaps disturbances other IEI, iii) potential cell-based therapies for dysregulation (https://doi.org/10.3389/fimmu.2023.1278759). non-systematic targeted literature review aimed at summarizing both diagnostic therapeutic approaches associated dysfunction. Tregs, particularly those committed thymus (tTregs), play non-redundant role control autoimmune inflammatory diseases, is critical identify relevant network epigenomic interactions governing tTregs their possible alterations IEI. Sousa et al. used genome-wide expression (RNA-seq) chromatin accessibility maps (ATAC-seq) purified CD4 single-positive (CD4SP) Tregs conventional (Tconv) from human thymuses define signature quantify transcription factor (TF) binding (http://doi.org/10.3389/fimmu.2024.1458581). Applying an artificial intelligence approach, they uncovered main Gene Modules (GRM) shaping identity thymus. The identified playing key regulation processes. also explored GRMs thymic decipher disorders, analyzing mutational hotspots cohort patients Common Variable Immunodeficiency (CVID), most frequent symptomatic (PID) featuring manifestations, not yet monogenic mutations. CVID characterized decreased classswitched memory B (4) but manifestations -that low levels -can occur (5). study results demonstrated -for large majority GRM -a higher prevalence (http://doi.org/10.3389/fimmu.2024.1458581).Tregs been Predominantly Antibody Deficiencies (PADs), poor antibody responses, increased susceptibility infections chronic (6). Immunoglobulin G subclass deficiency (IgGsd) mild PAD frequencies reduced least one IgG subclass. Most IgGsd had or several comorbidities such atopy, lung function.Interestingly, Wågström colleagues, lower activated were observed, partly restored during immunoglobulin replacement therapy (IgGRT), thus suggesting involvement pathogenesis development PADs (https://doi.org/10.3389/fimmu.2024.1442749 ). Another aspect field concerns (Bregs), widely accepted important modulatory component that suppresses cell differentiation promotes peripheral tolerance. Indeed, breakdown activity autoimmunity immunodeficiency (7,8). Although PIRDs earlyonset date there limited reference values populations (Tregs Bregs) pediatric population, terms phenotypic functional characterization. Topic collection, Luo describe changes Bregs observed healthy population showing abundant before age 7 3, respectively; evidence reinforces concept immunotolerance process mainly occurs early childhood (https://doi.org/10.3389/fimmu.2023.1283981 Pediatric PID requires more detailed assessment status because often develops age.Intriguingly, having paradoxically display autoreactive antibodies (i.e., anti-tTG, anti-DGP, anti-SS-B, anti-Sm) associate typically celiac disease (CD) (9). Hence, measurement autoantibodies might useful screening test diseases patients. association CD PIDs (i.e. sIgAD CVID) suggests shared pathomechanisms autoimmunity. includes dysregulated germ-center reactions together altered uncontrolled lymphocyte proliferation (10). Scarmozzino view refractory (RCD-I -II) enteropathy-associated T-cell lymphoma (EATL), two rare, severe, complications CD. RCD-I RCD-II stemming driven abnormal responses against glutenderived peptides genetically susceptible individuals (11). More detail, represents gluten-independent dysimmune reaction small bowel, can regarded aggressive situ high risk EATL progression. authors addressed biology clinical-pathological features conditions, highlighting unique patterns recurrent genetic events (https://doi.org/10.3389/fonc.2023.1273305). Disruptions epigenome increasingly being common pathogenic mechanism underlying rare (12). case Immunodeficiency, Centromeric instability Facial anomalies (ICF) syndrome, autosomal disorder hypogammaglobulinemia chromosomal accompanied DNA hypomethylation (13). ICF naïve lack B-cells plasma cells. some suffer viral fungal suspected concomitant immunodeficiency.While less common, subgroup exhibits abnormalities alongside B-cell anomalies, T-cells effector T-and follicular helper T-cells. Their pathological variant immunophenotype accurately recapitulated brief Unoki, intersection among epigenetics, repair, immunology (https://doi.org/10.3389/fimmu.2024.1405022). signaling B-cells, imbalance subsets, satellite RNA-mediated activation innate response potentially explain subset However, understanding molecular these still its initial stages. Strazzullo & Matarazzo novel model ICF-2 subtype 2 (ICF-2), due variants ZBTB24 gene (https://doi.org/10.3389/fimmu.2024.1419748). belonging Zinc-finger BTB domain-containing protein family, regulators developmental link between methylation errors elusive. By deriving induced pluripotent stem (iPSCs) CD34 + -blood patient, generated highly explore homeostasis, providing tool investigate linking ICF2 clinical (https://doi.org/10.3389/fimmu.2024.1419748) . dissecting relationship causative phenotypes disorders.Overall, provides increase our system pave way interventions improve lives perhaps related -more -immune diseases.

Language: Английский