CD103 integrin identifies a high IL‐10‐producing FoxP3⁺regulatory T‐cell population suppressing allergic airway inflammation

Abstract

Background Although FoxP3+ regulatory T (Treg) cells constitute a highly heterogeneous population, with different regulatory potential depending on the disease context, distinct subsets or phenotypes remain poorly defined. This hampers the development of immunotherapy for allergic and autoimmune disorders. The present study aimed at characterizing distinct FoxP3+ Treg subpopulations involved in the suppression of Th2‐mediated allergic inflammation in the lung. Methods We used an established mouse model of allergic airway disease based on ovalbumin sensitization and challenge to analyze FoxP3+ Tregs during the induction and resolution of inflammation, and identify markers that distinguish their most suppressive phenotypes. We also developed a new knock‐in mouse model (Foxp3creCd103dtr) enabling the specific ablation of CD103+FoxP3+ Tregs for functional studies. Results We found that during resolution of allergic airway inflammation in mice >50% of FoxP3+ Treg cells expressed the integrin CD103 which marks FoxP3+ Treg cells of high IL‐10 production, increased expression of immunoregulatory molecules such as KLRG1, ICOS and CD127, and enhanced suppressive capacity for Th2‐mediated inflammatory responses. CD103+FoxP3+ Tregs were essential for keeping allergic inflammation under control as their specific depletion in Foxp3creCd103dtr mice lead to severe alveocapillary damage, eosinophilic pneumonia, and markedly reduced lifespan of the animals. Conversely, adoptive transfer of CD103+FoxP3+ Tregs effectively treated disease, attenuating Th2 responses and allergic inflammation in an IL‐10‐dependent manner. Conclusions Our study identifies a novel regulatory T‐cell population, defined by CD103 expression, programmed to prevent exuberant type 2 inflammation and keep homeostasis in the respiratory tract under control. This has important therapeutic implications.

Plasma Metabolites and Gut Microbiota Are Associated With T cell Imbalance in BALB/c Model of Eosinophilic Asthma

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The Inhibitory Effect of Regulatory T Cells on the Intimal Hyperplasia of Tissue-Engineered Blood Vessels in Diabetic Pigs

“…Treg cells highly express HLA-G and CTLA-4, which can inhibit the proliferation and activation of immune cells through direct contact or exosome ( Hao et al, 2007 ; Zhang et al, 2018 ; Rana and Biswas, 2020 ). Treg cells can also secrete IL-10 and TGF-β, indirectly exerting biological functions ( Song et al, 2021 ; Tagkareli et al, 2022 ). Clinical studies have shown that Treg cells are positively correlated with early EPCs, but the specific mechanism is unclear.…”

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

“…In the intestine, several factors including retinoic acid, TGF-β, short-chain fatty acids, or microbiota metabolites promote the generation of pTregs. In the lung, CD103 + FOXP3 + Tregs control immune responses to infections and restrict allergic responses through the suppression of Th2 responses [25]. Dendritic cells (DCs) are professional antigen-presenting cells that play a key role in the generation of pTregs.…”