| First Author | Wang Y | Year | 2014 |
| Journal | Lab Invest | Volume | 94 |
| Issue | 12 | Pages | 1312-25 |
| PubMed ID | 25365203 | Mgi Jnum | J:216757 |
| Mgi Id | MGI:5609485 | Doi | 10.1038/labinvest.2014.126 |
| Citation | Wang Y, et al. (2014) Exposure to cigarette smoke impacts myeloid-derived regulatory cell function and exacerbates airway hyper-responsiveness. Lab Invest 94(12):1312-25 |
| abstractText | Cigarette smoking enhances oxidative stress and airway inflammation in asthma, the mechanisms of which are largely unknown. Myeloid-derived regulatory cells (MDRC) are free radical producing immature myeloid cells with immunoregulatory properties that have recently been demonstrated as critical regulators of allergic airway inflammation. NO (nitric oxide)-producing immunosuppressive MDRC suppress T-cell proliferation and airway-hyper responsiveness (AHR), while the O2(*-) (superoxide)-producing MDRC are proinflammatory. We hypothesized that cigarette smoke (CS) exposure may impact MDRC function and contribute to exacerbations in asthma. Exposure of bone marrow (BM)-derived NO-producing MDRC to CS reduced the production of NO and its metabolites and inhibited their potential to suppress T-cell proliferation. Production of immunoregulatory cytokine IL-10 was significantly inhibited, while proinflammatory cytokines IL-6, IL-1beta, TNF-alpha and IL-33 were enhanced in CS-exposed BM-MDRC. Additionally, CS exposure increased NF-kappaB activation and induced BM-MDRC-mediated production of O2(*-), via NF-kappaB-dependent pathway. Intratracheal transfer of smoke-exposed MDRC-producing proinflammatory cytokines increased NF-kappaB activation, reactive oxygen species and mucin production in vivo and exacerbated AHR in C57BL/6 mice, mice deficient in Type I IFNR and MyD88, both with reduced numbers of endogenous MDRC. Thus CS exposure modulates MDRC function and contributes to asthma exacerbation and identifies MDRC as potential targets for asthma therapy. |
