Surfactant protein A modulates induction of regulatory T cells via TGF-β.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Mukherjee, S; Giamberardino, C; Thomas, JM; Gowdy, K; Pastva, AM; Wright, JR
Published Date
- May 1, 2012
Published In
Volume / Issue
- 188 / 9
Start / End Page
- 4376 - 4384
PubMed ID
- 22474025
Pubmed Central ID
- PMC3331948
Electronic International Standard Serial Number (EISSN)
- 1550-6606
Digital Object Identifier (DOI)
- 10.4049/jimmunol.1101775
Language
- eng
Conference Location
- United States