title: Surfactant protein A modulates induction of regulatory T cells via TGF-β.
abstract: TCR signaling plays a critical role in regulatory T cell (Treg) development. However, the mechanism for tissue-specific induction of Tregs in the periphery remains unclear. We observed that surfactant protein A (SP-A)-deficient mice have impaired expression of Foxp3 and fewer CD25(+)Foxp3(+) Tregs after ex vivo stimulation and after stimulation with LPS in vivo. The addition of exogenous SP-A completely reversed this phenotype. Although SP-A is known to inhibit T cell proliferation under certain activation conditions, both IL-2 levels as well as active TGF-β levels increase on extended culture with exogenous SP-A, providing a key mechanism for the maintenance and induction of Tregs. In addition, kinetic suppression assays demonstrate that SP-A enhances the frequency of functional Foxp3(+) Tregs in responder T cell populations in a TGF-β-dependent manner. In mice treated with LPS in vivo, Tregs increased ∼160% in wild-type mice compared with only a 50% increase in LPS-treated SP-A(-/-) mice 8 d after exposure. Taken together, these findings support the hypothesis that SP-A affects T cell immune function by the induction of Tregs during activation.
authors.affiliation: Department of Cell Biology, Duke University Medical Center, Durham NC 27710, USA.
authors.forename: Sambuddho
authors.initials: S
authors.lastname: Mukherjee
authors.forename: Charles
authors.initials: C
authors.lastname: Giamberardino
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Thomas
authors.forename: Kymberly
authors.initials: K
authors.lastname: Gowdy
authors.forename: Amy M
authors.initials: AM
authors.lastname: Pastva
authors.forename: Jo Rae
authors.initials: JR
authors.lastname: Wright
mesh_terms: D000818:Animals; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D037662:Pulmonary Surfactant-Associated Protein A / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007376:Interleukin-2; D008070:Lipopolysaccharides; D037662:Pulmonary Surfactant-Associated Protein A