Regulatory T cells and their roles in immune dysregulation and allergy

Abstract

The main function of the immune system is to fight off potential infections, but also to maintain its activity below a level that would trigger self-reactivity. Regulatory T cells (Tregs) such as forkhead box P3(+) (FOXP3) Tregs and type 1 regulatory T cells (Tr1) play an essential role in this active process, using several distinct suppressive mechanisms. A wide range of pathologies have been associated with altered Treg cell function. This is best exemplified by the impact of mutations of genes essential for Treg function and the associated autoimmune syndromes. This review summarizes the main features of different subtypes of Tregs and focuses on the clinical implications of their altered function in human studies. More specifically, we discuss abnormalities affecting FOXP3(+) Tregs and Tr1 cells that will lead to autoimmune manifestations and/or allergic reactions, and the potential therapeutic use of Tregs.

Fig. 1

FOXP3⁺ cells in healthy and pathologic conditions. a Healthy FOXP3⁺ regulatory T cells (Tregs) express the IL-2 receptor CD25, CTLA4 and the transcription factors STAT5 and FOXP3. Genetic abnormalities of these molecules are associated with Treg dysfunction: b FOXP3 mutations are causative for the immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. c, d Mutations of CD25 and STAT5 are responsible for the development of immunodeficiency with autoimmunity related to IPEX. e Polymorphisms of CTLA4 have been associated with polyautoimmune pathologies. f Polymorphisms of the FOXP3 gene have been observed in allergic patients, suggesting a causative link