| First Author | Hung CH | Year | 2004 |
| Journal | J Allergy Clin Immunol | Volume | 114 |
| Issue | 3 | Pages | 664-70 |
| PubMed ID | 15356574 | Mgi Jnum | J:105523 |
| Mgi Id | MGI:3615741 | Doi | 10.1016/j.jaci.2004.05.042 |
| Citation | Hung CH, et al. (2004) Regulation of TH2 responses by the pulmonary Clara cell secretory 10-kd protein. J Allergy Clin Immunol 114(3):664-70 |
| abstractText | 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. |
