| First Author | Koh B | Year | 2020 |
| Journal | J Allergy Clin Immunol | Volume | 146 |
| Issue | 5 | Pages | 1121-1136.e9 |
| PubMed ID | 32179158 | Mgi Jnum | J:304734 |
| Mgi Id | MGI:6693934 | Doi | 10.1016/j.jaci.2020.03.002 |
| Citation | Koh B, et al. (2020) Bcl6 and Blimp1 reciprocally regulate ST2(+) Treg-cell development in the context of allergic airway inflammation. J Allergy Clin Immunol 146(5):1121-1136.e9 |
| abstractText | BACKGROUND: Bcl6 is required for the development of T follicular helper cells and T follicular regulatory (Tfr) cells that regulate germinal center responses. Bcl6 also affects the function of regulatory T (Treg) cells. OBJECTIVE: The goal of this study was to define the functions of Bcl6 in Treg cells, including Tfr cells, in the context of allergic airway inflammation. METHODS: We used a model of house dust mite sensitization to challenge wild-type, Bcl6(fl/fl) Foxp3-Cre, and Prdm1 (Blimp1)(fl/fl) Foxp3-Cre mice to study the reciprocal roles of Bcl6 and Blimp1 in allergic airway inflammation. RESULTS: In the house dust mite model, Tfr cells repress the production of IgE and Bcl6(+) Treg cells suppress the generation of type 2 cytokine-producing cells in the lungs. In mice with Bcl6-deficient Treg cells, twice as many ST2(+) (IL-33R(+)) Treg cells develop as are observed in wild-type mice. ST2(+) Treg cells in the context of allergic airway inflammation are Blimp1 dependent, express type 2 cytokines, and share features of visceral adipose tissue Treg cells. Bcl6-deficient Treg cells are more susceptible, and Blimp1-deficient Treg cells are resistant, to acquiring the ST2(+) Treg-cell phenotype in vitro and in vivo in response to IL-33. Bcl6-deficient ST2(+) Treg cells, but not Bcl6-deficient ST2(+) conventional T cells, strongly promote allergic airway inflammation when transferred into recipient mice. Lastly, ST2 is required for the exacerbated allergic airway inflammation in Bcl6(fl/fl) Foxp3-Cre mice. CONCLUSIONS: During allergic airway inflammation, Bcl6 and Blimp1 play dual roles in regulating Tfr-cell activity in the germinal center and in the development of ST2(+) Treg cells that promote type 2 cytokine responses. |
