| Autor: |
Pedro H. Gazzinelli-Guimaraes, PhD, Dominic P. Golec, PhD, Erik P. Karmele, PhD, Joshua Sciurba, BSc, Pablo Bara-Garcia, MSc, Tom Hill, PhD, Byunghyun Kang, PhD, Sasisekhar Bennuru, PhD, Pamela L. Schwartzberg, MD, Thomas B. Nutman, MD |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
Journal of Allergy and Clinical Immunology: Global, Vol 2, Iss 4, Pp 100131- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2772-8293 |
| DOI: |
10.1016/j.jacig.2023.100131 |
| Popis: |
Background: The immunologic mechanisms underlying pulmonary type 2 inflammation, including the dynamics of eosinophil recruitment to the lungs, still need to be elucidated. Objective: We sought to investigate how IL-13–producing TH2 effector cells trigger eosinophil migration in house dust mite (HDM)-driven allergic pulmonary inflammation. Methods: Multiparameter and molecular profiling of murine lungs with HDM-induced allergy was investigated in the absence of IL-13 signaling by using IL-13Rα1–deficient mice and separately through adoptive transfer of CD4+ T cells from IL-5–deficient mice into TCRα–/– mice before allergic inflammation. Results: We demonstrated through single-cell techniques that HDM-driven pulmonary inflammation displays a profile characterized by TH2 effector cell–induced IL-13–dominated eosinophilic inflammation. Using HDM-sensitized IL-13Rα1–/– mice, we found a marked reduction in the influx of eosinophils into the lungs along with a significant downregulation of both CCL-11 and CCL-24. We further found that eosinophil trafficking to the lung relies on production of IL-13–driven CCL-11 and CCL-24 by fibroblasts and Ly6C+ (so-called classical) monocytes. Moreover, this IL-13–mediated eotaxin-dependent eosinophil influx to the lung tissue required IL-5–induced eosinophilia. Finally, we demonstrated that this IL-13–driven eosinophil-dominated pulmonary inflammation was critical for limiting bystander lung transiting Ascaris parasites in a model of allergy and helminth interaction. Conclusion: Our data suggest that IL-5–dependent allergen-specific TH2 effector cell response and subsequent signaling through the IL-13/IL-13Rα1 axis in fibroblasts and myeloid cells regulate the eotaxin-dependent recruitment of eosinophils to the lungs, with multiple downstream consequences, including bystander control of lung transiting parasitic helminths. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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