WASP, Tregs, and food allergies - rare disease provides insight into a common problem

Abstract

Dysregulation of the type 2 immune system presents with various manifestations, including allergic inflammation, and has emerged as an alarming public health issue. The pathological mechanisms that underlie T helper type 2 cell-driven (Th2-driven) allergic diseases remain unclear. In particular, it is not completely understood how type 2 immunity is restricted in inflammatory responses. In this issue of the JCI, Lexmond et al. use Wiskott-Aldrich syndrome as a model disease and establish that the Wiskott-Aldrich gene product (WASP) serves an essential role in T regulatory cells to contain Th2 effector cell differentiation and prevent allergic sensitization to dietary antigens.

Figure 1. WASP functions in Tregs to contain Th2-mediated allergy.

(A) In WASP-expressing Tregs, GATA3 expression is repressed and thereby restrains Th2-type inflammation in response to food antigens. (B) Tregs lacking WASP, such as occurs in patients with mutations that lead to Wiskott-Aldrich syndrome and X-linked thrombocytopenia, are insufficient in restraining Th2-type inflammation in response to food allergens. This lack of Th2 suppression is associated with an increased frequency of GATA3^hi effector memory Tregs.