Basic and clinical immunologyRegulation of TH2 responses by the pulmonary Clara cell secretory 10-kd protein☆
Section snippets
Cell culture, in vitro T-cell polarization, and cytokine analysis
Spleen cells were isolated from 8-week-old Balb/c mice after 2 weekly intraperitoneal sensitizations with 10 μg ovalbumin (OVA; grade V; Sigma, St Louis, Mo) emulsified in 2 mg alum (Pierce, Rockford, Ill). To obtain CD4+ T cells, splenocytes were isolated from naive Balb/c mice 8 to 12 weeks old to >97% purity with positive selection by using anti-CD4 magnetic beads (Miltenyi Biotec, Auburn, Calif) according to the manufacturer's instructions. For in vitro TH1 and TH2 polarization,12 CD4+ T
Results
CC10 gene deficiency exacerbates pulmonary inflammation,8 which is associated with increased levels of TH2 cytokines, whereas no significant change in the number of infiltrating T cells is seen, suggesting a modulating effect of CC10 on the activation and/or cytokine expression of T cells. To determine the effect of CC10 on Ag-induced T-cell responses in vitro, spleen cells from OVA-sensitized mice were treated with varying doses of CC10 for 2 hours, followed by the stimulation of the cells
Discussion
In this report, we provide evidence that rCC10 is able selectively to inhibit the expression of TH2 cytokines and a critical TH2 transcriptional factor, GATA-3. Also, the suppression of GATA-3 expression is mediated, at least in part, by CC10-mediated alteration of mRNA stability. In addition, the results of in vivo studies demonstrated that mucosal CC10 gene transfer was able to inhibit pulmonary TH2 cytokine production and eosinophilia seen in CC10-deficient mice, providing evidence for a
Acknowledgements
We thank Dr. Anil Mukherjee for scientific input and advice during the course of this study.
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Association of serum CC16 levels with eosinophilic inflammation and respiratory dysfunction in severe asthma
2023, Respiratory MedicineCitation Excerpt :Sensitized mice with CC16 deficiency have a higher percentage of eosinophils and T-helper type 2 (Th2) markers such as interleukin (IL)-4, IL-5, IL-13, and eotaxin in bronchoalveolar fluid when compared to wild-type mice [17,18]. Further, the reconstitution of CC16 in CC16-deficient mice can reduce Th2 cytokines and pulmonary eosinophilia [18]. Therefore, the airway/circulatory levels of CC16 might potentially influence local inflammation in patients with severe asthma and might be used as a predictor of Th2 inflammation in the airway.
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This work was supported, in part, by National Institutes of Health (ROI-40274), Philip Morris USA Inc, National Science Council (Taiwan:NSC92-2314-B-182A-111), and Chang Gung Memorial Hospital, Taiwan (CMRP 1359).
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These authors contributed equally to this work.