All-trans retinoic acid and rapamycin synergize with transforming growth factor-?1 to induce regulatory T cells but confer different migratory capacities.

ABSTRACT: Tregs play important roles in maintaining immune homeostasis, and thus, therapies based on Treg are promising candidates for the treatment for a variety of immune-mediated disorders. These therapies, however, face the significant challenge of obtaining adequate numbers of Tregs from peripheral blood that maintains suppressive function following extensive expansion. Inducing Tregs from non-Tregs offers a viable alternative. Different methods to induce Tregs have been proposed and involve mainly treating cells with TGF-?-iTreg. However, use of TGF-? alone is not sufficient to induce stable Tregs. ATRA or rapa has been shown to synergize with TGF-? to induce stable Tregs. Whereas TGF-? plus RA-iTregs have been well-described in the literature, the phenotype, function, and migratory characteristics of TGF-? plus rapa-iTreg have yet to be elucidated. Herein, we describe the phenotype and function of mouse rapa-iTreg and reveal that these cells differ in their in vivo homing capacity when compared with mouse RA-iTreg and mouse TGF-?-iTreg. This difference in migratory activity significantly affects the therapeutic capacity of each subset in a mouse model of colitis. We also describe the characteristics of iTreg generated in the presence of TGF-?, RA, and rapa.

SUBMITTER: Jhunjhunwala S 

PROVIDER: S-EPMC3800062 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature