| First Author | Han M | Year | 2017 |
| Journal | Am J Respir Cell Mol Biol | Volume | 56 |
| Issue | 2 | Pages | 242-251 |
| PubMed ID | 27679954 | Mgi Jnum | J:257413 |
| Mgi Id | MGI:6115158 | Doi | 10.1165/rcmb.2016-0056OC |
| Citation | Han M, et al. (2017) IFN-gamma Blocks Development of an Asthma Phenotype in Rhinovirus-Infected Baby Mice by Inhibiting Type 2 Innate Lymphoid Cells. Am J Respir Cell Mol Biol 56(2):242-251 |
| abstractText | Early-life wheezing-associated infections with rhinovirus (RV) have been associated with asthma development in children. We have shown that RV infection of 6-day-old mice induces mucous metaplasia and airways hyperresponsiveness, which is dependent on IL-13, IL-25, and type 2 innate lymphoid cells (ILC2s). Infection of immature mice fails to induce lung IFN-gamma expression, in contrast to mature 8-week-old mice with a robust IFN-gamma response, consistent with the notion that deficient IFN-gamma production in immature mice permits RV-induced type 2 immune responses. We therefore examined the effects of intranasal IFN-gamma administration on RV-induced ILC2 expansion and IL-13 expression in 6-day-old BALB/c and IL-13 reporter mice. Airway responses were assessed by histology, immunofluorescence microscopy, quantitative polymerase chain reaction, ELISA, and flow cytometry. Lung ILC2s were also treated with IFN-gamma ex vivo. We found that, compared with untreated RV-infected immature mice, IFN-gamma treatment attenuated RV-induced IL-13 and Muc5ac mRNA expression and mucous metaplasia. IFN-gamma also reduced ILC2 expansion and the percentage of IL-13-secreting ILC2s. IFN-gamma had no effect on the mRNA or protein expression of IL-25, IL-33, or thymic stromal lymphoprotein. Finally, IFN-gamma treatment of sorted ILC2s reduced IL-5, IL-13, IL-17RB, ST2, and GATA-3 mRNA expression. We conclude that, in immature mice, IFN-gamma inhibits ILC2 expansion and IL-13 expression in vivo and ex vivo, thereby attenuating RV-induced mucous metaplasia. These findings demonstrate the antagonistic function of IFN-gamma on ILC2 expansion and gene expression, the absence of which may contribute to the development of an asthma-like phenotype after early-life RV infection. |
