Negative Regulation of Pulmonary Th17 Responses by C3a Anaphylatoxin during Allergic Inflammation in Mice

Hoyong Lim, Young Uk Kim, Scott M. Drouin, Stacey Mueller-Ortiz, Kyoungah Yun, E. Morschl, Rick A. Wetsel, Yeonseok Chung

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Activation of complement is one of the earliest immune responses to exogenous threats, resulting in various cleavage products including anaphylatoxin C3a. In addition to its contribution to host defense, C3a has been shown to mediate Th2 responses in animal models of asthma. However, the role of C3a on pulmonary Th17 responses during allergic inflammation remains unclear. Here, we show that mice deficient in C3a receptor (C3aR) exhibited (i) higher percentages of endogenous IL-17-producing CD4+ T cells in the lungs, (ii) higher amounts of IL-17 in the bronchoalveolar lavage fluid, and (iii) more neutrophils in the lungs than wild-type mice when challenged with intranasal allergens. Moreover, adoptive transfer experiments showed that the frequencies of antigen-specific IL-17-producing CD4+ T cells were significantly higher in the lungs and bronchial lymph nodes of C3aR-deficient recipients than those of wild-types recipients. Bone-marrow reconstitution study indicated that C3aR-deficiency on hematopoietic cells was required for the increased Th17 responses. Furthermore, C3aR-deficient mice exhibited increased percentages of Foxp3+ regulatory T cells; however, depletion of these cells minimally affected the induction of antigen-specific Th17 cell population in the lungs. Neutralization of IL-17 significantly reduced the number of neutrophils in bronchoalveolar lavage fluid of C3aR-deficient mice. Our findings demonstrate that C3a signals negatively regulate antigen-specific Th17 responses during allergic lung inflammation and the size of Foxp3+ regulatory T cell population in the periphery.

Original languageEnglish
Article numbere52666
JournalPLoS One
Volume7
Issue number12
DOIs
Publication statusPublished - Dec 20 2012

Fingerprint

Anaphylatoxins
T-cells
Interleukin-17
inflammation
lungs
Inflammation
Lung
mice
T-lymphocytes
receptors
Antigens
Bronchoalveolar Lavage Fluid
Regulatory T-Lymphocytes
antigens
Neutrophils
Fluids
neutrophils
T-Lymphocytes
Th17 Cells
Allergens

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Negative Regulation of Pulmonary Th17 Responses by C3a Anaphylatoxin during Allergic Inflammation in Mice. / Lim, Hoyong; Kim, Young Uk; Drouin, Scott M.; Mueller-Ortiz, Stacey; Yun, Kyoungah; Morschl, E.; Wetsel, Rick A.; Chung, Yeonseok.

In: PLoS One, Vol. 7, No. 12, e52666, 20.12.2012.

Research output: Contribution to journalArticle

Lim, H, Kim, YU, Drouin, SM, Mueller-Ortiz, S, Yun, K, Morschl, E, Wetsel, RA & Chung, Y 2012, 'Negative Regulation of Pulmonary Th17 Responses by C3a Anaphylatoxin during Allergic Inflammation in Mice', PLoS One, vol. 7, no. 12, e52666. https://doi.org/10.1371/journal.pone.0052666
Lim, Hoyong ; Kim, Young Uk ; Drouin, Scott M. ; Mueller-Ortiz, Stacey ; Yun, Kyoungah ; Morschl, E. ; Wetsel, Rick A. ; Chung, Yeonseok. / Negative Regulation of Pulmonary Th17 Responses by C3a Anaphylatoxin during Allergic Inflammation in Mice. In: PLoS One. 2012 ; Vol. 7, No. 12.
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