Regulation of TH2 responses by the pulmonary Clara cell secretory 10-kd protein

J Allergy Clin Immunol. 2004 Sep;114(3):664-70. doi: 10.1016/j.jaci.2004.05.042.


Background: Pulmonary Clara cell secretory 10-kd protein (CC10) is a steroid-inducible and potentially anti-inflammatory cytokine, but its direct involvement in the regulation of T-cell responses remains unknown.

Objective: The role of CC10 in the regulation of T(H)2 cytokine expression was investigated.

Methods: The levels of cytokine and GATA-3 expression were determined by ELISA and RT-PCR, respectively. Bronchoalveolar lavage fluid cell counts were also determined by using a standard protocol. CC10 expression in vivo was determined by immunocytochemistry and Western blotting.

Results: In vitro, a significant, dose-dependent suppressive effect of CC10 was found on T(H)2 cytokine expression, but not IFN-gamma, in splenocytes of antigen-sensitized mice. A similar suppressive effect was also noted in polarized CD4(+) T(H)2 cells, but not in naive CD4(+) T cells. In contrast, CC10 was able to induce IFN-gamma expression in naive CD4(+) T cells, but not in polarized T(H)1 cells. Furthermore, the suppression of T(H)2 cytokine expression was concomitant with reduction of a critical transcription factor, GATA-3. Of significance was the finding that although no significant change was found in the decay kinetics of T(H)2 cytokine transcripts, a significant decrease in mRNA stability of GATA-3 was seen in CC10-treated cells. In vivo, reconstitution of the CC10 gene in CC10-deficient mice resulted in significantly lower levels of T(H)2 cytokines, concomitant with a decrease in GATA-3 expression, after challenge with Ag compared with those seen in mock-transduced mice, which are associated with reduced levels of pulmonary eosinophilia.

Conclusion: These results demonstrate, that CC10 plays a direct role in the regulation of T-cell-mediated inflammatory responses.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Gene Expression Regulation*
  • Lung / immunology*
  • Lung / metabolism
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Recombinant Proteins / immunology
  • Spleen / cytology
  • Spleen / immunology
  • Th2 Cells / immunology*
  • Uteroglobin / genetics
  • Uteroglobin / metabolism*


  • Cytokines
  • Recombinant Proteins
  • Scgb1a1 protein, mouse
  • Uteroglobin