A novel role of the pulmonary Clara cell secretory 10 kD protein (CC10) in the regulation of T-cell responses

Abstract

Rationale Pulmonary Clara cell secretory protein, CC10, is a steroid-inducible and potentially anti-inflammatory cytokine, but its direct involvement in the regulation of T cell responses remains unknown. Methods Mouse CD4 + T cells were isolated from Balb/c mice with positive selection using anti-CD4 magnetic beads and polarized into Th1 and Th2 conditions. Cells were stimulated with 1 μg/ml of anti-CD3 and 1 μg/ml of anti-CD28 mAbs with or without the pre-treatment of the cells with varying doses of recombinant CC10 (rCC10; 0.3-300 ng/ml) for 2 hrs. Cells were harvested at 4, 6, and 24 hours for RT-PCR, Western blot and ELISA to detect the changes in Th2 cytokines and IFN-γ. Results A significant, dose-dependent suppressive effect of CC10 on Th2 cytokine expression (IL-4, IL-5 and IL-13) was seen in polarized CD4 + Th2 cells, but not in naive CD4 + T cells. In contrast, CC10 was able to induce IFN-γ expression in naive CD4 + T cells, but not in polarized Th1 cells. Furthermore, the suppression of Th2 cytokine expression is concomitant with reduction of a critical transcription factor, GATA-3. Of significance is the finding that while no significant change was found in the decay kinetics of Th2 cytokine transcripts, a significant decrease in mRNA stability of GATA-3 was seen in CC10-treated cells. Conclusions These results suggest that CC10 plays a direct role in the regulation of T cell-mediated inflammatory responses.