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J Immunol. 2012 May 1;188(9):4376-84. doi: 10.4049/jimmunol.1101775. Epub 2012 Apr 2.

Surfactant protein A modulates induction of regulatory T cells via TGF-β.

Author information

1
Department of Cell Biology, Duke University Medical Center, Durham NC 27710, USA.

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.

PMID:
22474025
PMCID:
PMC3331948
DOI:
10.4049/jimmunol.1101775
[Indexed for MEDLINE]
Free PMC Article

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