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.
Objective: This 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 (
Foxp3Cd103) 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
Foxp3Cd103 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. Conclusion: 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.
Androgen Receptor Signaling Augments Regulatory T Cell Functions to Attenuate Allergic Airway Inflammation