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

Publication ,  Journal Article
Mukherjee, S; Giamberardino, C; Thomas, JM; Gowdy, K; Pastva, AM; Wright, JR
Published in: J Immunol
May 1, 2012

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.

Duke Scholars

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

May 1, 2012

Volume

188

Issue

9

Start / End Page

4376 / 4384

Location

United States

Related Subject Headings

  • T-Lymphocytes, Regulatory
  • Pulmonary Surfactant-Associated Protein A
  • Mice, Knockout
  • Mice
  • Lymphocyte Activation
  • Lipopolysaccharides
  • Interleukin-2
  • Immunology
  • Gene Expression Regulation
  • Forkhead Transcription Factors
 

Citation

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Mukherjee, S., Giamberardino, C., Thomas, J. M., Gowdy, K., Pastva, A. M., & Wright, J. R. (2012). Surfactant protein A modulates induction of regulatory T cells via TGF-β. J Immunol, 188(9), 4376–4384. https://doi.org/10.4049/jimmunol.1101775
Mukherjee, Sambuddho, Charles Giamberardino, Joseph M. Thomas, Kymberly Gowdy, Amy M. Pastva, and Jo Rae Wright. “Surfactant protein A modulates induction of regulatory T cells via TGF-β.J Immunol 188, no. 9 (May 1, 2012): 4376–84. https://doi.org/10.4049/jimmunol.1101775.
Mukherjee S, Giamberardino C, Thomas JM, Gowdy K, Pastva AM, Wright JR. Surfactant protein A modulates induction of regulatory T cells via TGF-β. J Immunol. 2012 May 1;188(9):4376–84.
Mukherjee, Sambuddho, et al. “Surfactant protein A modulates induction of regulatory T cells via TGF-β.J Immunol, vol. 188, no. 9, May 2012, pp. 4376–84. Pubmed, doi:10.4049/jimmunol.1101775.
Mukherjee S, Giamberardino C, Thomas JM, Gowdy K, Pastva AM, Wright JR. Surfactant protein A modulates induction of regulatory T cells via TGF-β. J Immunol. 2012 May 1;188(9):4376–4384.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

May 1, 2012

Volume

188

Issue

9

Start / End Page

4376 / 4384

Location

United States

Related Subject Headings

  • T-Lymphocytes, Regulatory
  • Pulmonary Surfactant-Associated Protein A
  • Mice, Knockout
  • Mice
  • Lymphocyte Activation
  • Lipopolysaccharides
  • Interleukin-2
  • Immunology
  • Gene Expression Regulation
  • Forkhead Transcription Factors