# Tumor necrosis factor receptor 2 in allergen tolerance: a perspective view

## TL;DR

This paper explores how TNFR2 contributes to immune tolerance and allergic inflammation, suggesting it as a potential target for allergy treatments.

## Contribution

The paper provides a comprehensive review of TNFR2's role in allergen tolerance and its potential as a novel therapeutic target.

## Key findings

- TNFR2 is crucial for promoting and maintaining immune tolerance.
- Immune checkpoints like TNFR2 are critical for understanding and treating allergic diseases.
- TNFR2 signaling pathways may offer new immunomodulatory treatment strategies for allergies.

## Abstract

Central and peripheral tolerance are key to maintain immune homeostasis. Imbalance of these processes often leads to diseases such as allergy, cancer or autoimmune disorders. During the immune response to allergens, several regulatory immune cells play a role in the development of peripheral tolerance and maintenance of homeostasis by inhibiting the development of CD4+ type 2 helper T cells, impairing the production of pro-allergenic cytokines, reducing the activation of effector cells driving allergic inflammation and generating allergen-neutralizing antibodies. However, the precise mechanisms of how peripheral immune tolerance is effectively maintained in healthy people, but not in allergic patients are still not well understood. Immune checkpoints have recently been proposed as critical molecular pathways across diseases for understanding how the immune system maintains homeostasis in many pathologies such as cancer, type 1 diabetes, multiple sclerosis, Crohn’s disease and allergy, among others. Particularly in the context of allergy, in-depth studies on immune checkpoint pathways might lead to emerging therapeutic targets. Tumor necrosis factor receptor 2 (TNFR2) is a crucial protein involved in promotion, expansion and maintenance of immune tolerance, being suggested as a key target for the treatment of several immune-based diseases including allergy. Here, we review the involvement of TNFR2 in allergic inflammation and allergen tolerance, its structural properties, signaling pathways, and importance for immune tolerance as a common mechanism, with the focus on possible implications for novel immunomodulatory treatments of allergic diseases.