Dysregulation of the Immune Response in TGF-β Signalopathies

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2022 Dec 26

PMID 36569843

Authors

Marco M Rodari

Nadine Cerf-Bensussan

Marianna Parlato

Affiliations

Soon will be listed here.

Abstract

The transforming growth factor-β (TGF-β) family of cytokines exerts pleiotropic functions during embryonic development, tissue homeostasis and repair as well as within the immune system. Single gene defects in individual component of this signaling machinery cause defined Mendelian diseases associated with aberrant activation of TGF-β signaling, ultimately leading to impaired development, immune responses or both. Gene defects that affect members of the TGF-β cytokine family result in more restricted phenotypes, while those affecting downstream components of the signaling machinery induce broader defects. These rare disorders, also known as TGF-β signalopathies, provide the unique opportunity to improve our understanding of the role and the relevance of the TGF-β signaling in the human immune system. Here, we summarize this elaborate signaling pathway, review the diverse clinical presentations and immunological phenotypes observed in these patients and discuss the phenotypic overlap between humans and mice genetically deficient for individual components of the TGF-β signaling cascade.

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