Treg in inborn errors of immunity: gaps, knowns and future perspectives

Front Immunol. 2024 Jan 8:14:1278759. doi: 10.3389/fimmu.2023.1278759. eCollection 2023.

Abstract

Regulatory T cells (Treg) are essential for immune balance, preventing overreactive responses and autoimmunity. Although traditionally characterized as CD4+CD25+CD127lowFoxP3hi, recent research has revealed diverse Treg subsets such as Tr1, Tr1-like, and CD8 Treg. Treg dysfunction leads to severe autoimmune diseases and immune-mediated inflammatory disorders. Inborn errors of immunity (IEI) are a group of disorders that affect correct functioning of the immune system. IEI include Tregopathies caused by genetic mutations affecting Treg development or function. In addition, Treg dysfunction is also observed in other IEIs, whose underlying mechanisms are largely unknown, thus requiring further research. This review provides a comprehensive overview and discussion of Treg in IEI focused on: A) advances and controversies in the evaluation of Treg extended subphenotypes and function; B) current knowledge and gaps in Treg disturbances in Tregopathies and other IEI including Treg subpopulation changes, genotype-phenotype correlation, Treg changes with disease activity, and available therapies, and C) the potential of Treg cell-based therapies for IEI with immune dysregulation. The aim is to improve both the diagnostic and the therapeutic approaches to IEI when there is involvement of Treg. We performed a non-systematic targeted literature review with a knowledgeable selection of current, high-quality original and review articles on Treg and IEI available since 2003 (with 58% of the articles within the last 6 years) in the PubMed database.

Keywords: Helios; IPEX syndrome; Treg; cell-based therapies; immune dysregulation; immune tolerance; primary immune regulatory disorders; primary immunodeficiency.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoimmune Diseases*
  • Autoimmunity
  • Databases, Factual
  • Humans
  • Mutation
  • T-Lymphocytes, Regulatory*

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the projects PI18/00223, FI19/00208, and PI21/00211 to LA, integrated in the Plan Nacional de I+D+I and cofinanced by the ISCIII -Subdirección General de Evaluación y Formento de la Investigación Sanitaria -and the Fondo Europeo de Desarrollo Regional (FEDER), by Pla Estratègic de Recerca i Innovació en Salut (PERIS), Departament de Salut, Generalitat de Catalunya (SLT006/17/00199 to LA), by a 2017 Leonardo Grant for Researchers and Cultural Creators, BBVA Foundation [IN(17)_BBM_CLI_0357] to LA, by a 2017 Beca de Investigación de la Sociedad Española De Inmunología Clínica Alergología y Asma Pediátrica to LA, by a 2022 Convocatòria de Beques de Recerca IRSJD -Carmen de Torres 2022 (2022AR-IRSJD-CdTorres) and CERCA Programme/Generalitat de Catalunya. It was also supported by grants from “Fundación Familia Alonso” (FFA-2019), from Instituto de Salud Carlos III (ISCIII) co-financed by FEDER funds (ICI20/00063; PI21/00189) granted to RCR. RKB is supported by research funds from IISGM. Project PI21/01325 was granted to ES-R and also supported this study.