Regulatory T Cell-Targeted Immunomodulatory Therapy for Long-Term Clinical Improvement of Atopic Dermatitis: Hypotheses and Perspectives

Abstract

Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disorder characterized by itching and eczematous lesions. It is often associated with a personal or familial history of allergic diseases. Allergic inflammation induced by immunoglobulin E and T-helper type 2 (Th2) cell responses to common environmental agents has been suggested to play an essential role in AD pathogenesis. The standard therapies for AD, including topical or systemic agents, focus on controlling skin inflammation. Recently developed monoclonal antibody to interleukin-4 receptor alpha or Janus kinase inhibitors can provide significant clinical improvements in patients with AD by inhibiting Th2 cell-mediated skin inflammation. However, the clinical efficacy of the Th2 cell-targeted therapy is transient and incomplete in patients with AD. Patients with AD are seeking a permanent cure. Therefore, the development of novel immunomodulatory strategies that can improve a long-term clinical outcome and provide a long-term treatment-free clinical remission of AD (disease-modifying therapy) is needed. Regulatory T (Treg) cells play a critical role in the maintenance of immune tolerance and suppress the development of autoimmune and allergic diseases. This review provides three working hypotheses and perspectives for the treatment of AD by Treg cell activation. (1) A decreased number or function of Treg cells is a critical event that causes the activation of Th2 cells, leading to the development and maintenance of AD. (2) Activation of Treg cells is an effective therapeutic approach for AD. (3) Many different immunomodulatory strategies activating Treg cells can provide a long-term clinical improvement of AD by induction of immune tolerance. The Treg cell-targeted immunomodulatory therapies for AD include allergen immunotherapy, microbiota, vitamin D, polyvalent human immunoglobulin G, monoclonal antibodies to the surface antigens of T cell or antigen-presenting cell, and adoptive transfer of autologous Treg cells or genetically engineered Treg cells expanded in vitro.

Acupoint Autohemotherapy Attenuates DNCB-Induced Atopic Dermatitis and Activates Regulatory T Cells in BALB/c Mice

“…Intramuscularly administered IgG might be processed by dendritic cells and activate anti-idiotypic Treg cells and improve the AD as recently suggested. 35 , 36 The effects of Treg and Th1 cell activation, however, were not observed with heterologous total IgG (naïve IgG) acupoint injections.…”

The Role of Regulatory T Cells in Allergic Diseases: Collegium Internationale Allergologicum (CIA) Update 2024

“…The ability of Tregs to regulate immune responses and their capacity to infiltrate the skin make them a potential player in the development of AD [167]. Studies of genetic disorders that affect Treg function have provided compelling evidence for their involvement in AD.…”

Targeting tumor-infiltrating tregs for improved antitumor responses

“…However, it’s important to note that the immunosuppressive activity of Tregs also plays a critical role in maintaining immune balance and tolerance in the body. There is growing research interest in harnessing the suppressive functions of Tregs to reduce immune rejection in organ transplantation and to treat allergic or autoimmune diseases that are often caused by excessive immune activation ( 123 – 125 ). Treg can also be adopted to minimize immune-related adverse events (irAEs) in cancer immunotherapy.…”