title: All-trans retinoic acid and rapamycin synergize with transforming growth factor-β1 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-β-iTreg. However, use of TGF-β alone is not sufficient to induce stable Tregs. ATRA or rapa has been shown to synergize with TGF-β to induce stable Tregs. Whereas TGF-β plus RA-iTregs have been well-described in the literature, the phenotype, function, and migratory characteristics of TGF-β 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-β-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-β, RA, and rapa.
authors.affiliation: 3.720 Rutland Ave, Room 755A, Baltimore, MD 21205, USA. g.raimondi@jhmi.edu or University of Pittsburgh, 3700 O'Hara St., 440 Benedum Hall, Pittsburgh, PA 15261, USA. E-mail: srlittle@pitt.edu; Twitter: http://www.twitter.com/@think_little.
authors.forename: Siddharth
authors.initials: S
authors.lastname: Jhunjhunwala
authors.forename: Leo C
authors.initials: LC
authors.lastname: Chen
authors.forename: Erin E
authors.initials: EE
authors.lastname: Nichols
authors.forename: Angus W
authors.initials: AW
authors.lastname: Thomson
authors.forename: Giorgio
authors.initials: G
authors.lastname: Raimondi
authors.forename: Steven R
authors.initials: SR
authors.lastname: Little
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D002465:Cell Movement / Q000187:drug effects; D004357:Drug Synergism; D039001:Integrin alpha Chains / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D054388:Receptors, CCR / Q000032:analysis; D020123:Sirolimus / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000502:physiology; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D015703:Antigens, CD; C119309:CC chemokine receptor 9; D039001:Integrin alpha Chains; D054388:Receptors, CCR; D053773:Transforming Growth Factor beta1; C091367:alpha E integrins; D014212:Tretinoin; D020123:Sirolimus
keywords: Treg migration; adoptive cell therapy; chemokines; inflammatory bowel disease; live-animal imaging
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