| First Author | Yamana T | Year | 2021 |
| Journal | J Immunol | Volume | 206 |
| Issue | 2 | Pages | 355-365 |
| PubMed ID | 33310873 | Mgi Jnum | J:303886 |
| Mgi Id | MGI:6515395 | Doi | 10.4049/jimmunol.2000198 |
| Citation | Yamana T, et al. (2021) IL-17A-Secreting Memory gammadelta T Cells Play a Pivotal Role in Sensitization and Development of Hypersensitivity Pneumonitis. J Immunol 206(2):355-365 |
| abstractText | Hypersensitivity pneumonitis (HP) typically presents with interstitial inflammation and granulomas induced by an aberrant immune response to inhaled Ags in sensitized individuals. Although IL-17A is involved in the development of HP, the cellular sources of IL-17A and the mechanisms by which IL-17A contributes to granuloma formation remain unclear. Recent studies report that gammadelta T cells produce IL-17A and exhibit memory properties in various diseases. Therefore, we focused on IL-17A-secreting memory gammadelta T cells in the sensitization phase and aimed to elucidate the mechanisms by which IL-17A contributes to granuloma formation in HP. We induced a mouse model of HP using pigeon dropping extract (PDE) in wild-type and IL-17A knockout (IL-17A(-/-)) mice. IL-17A(-/-) mice exhibited reduced granulomatous areas, attenuated aggregation of CD11b(+) alveolar macrophages, and reduced levels of CCL2, CCL4, and CCL5 in the bronchoalveolar lavage fluid. Among IL-17A(+) cells, more gammadelta T cells than CD4(+) cells were detected after intranasal PDE administration. Interestingly, the expansion of IL-17A-secreting Vgamma4(+) or Vgamma1(-)Vgamma4(-) cells of convalescent mice was enhanced in response to the sensitizing Ag. Additionally, coculture of macrophages with PDE and Vgamma4(+) cells purified from PDE-exposed convalescent mice produced significantly more IL-17A than coculture with Vgamma4(+) cells from naive mice. Our findings demonstrate that in the sensitization phase of HP, IL-17A-secreting memory gammadelta T cells play a pivotal role. Furthermore, we characterized the IL-17A/CCL2, CCL4, CCL5/CD11b(+) alveolar macrophage axis, which underlies granuloma formation in HP. These findings may lead to new clinical examinations or therapeutic targets for HP. |
