Eosinophils downregulate lung alloimmunity by decreasing TCR signal transduction
| Autor: | Bayan Mahgoub, Dongge Li, Andrew E. Gelman, Yizhan Guo, Anirban Banerjee, Adam G. Schrum, Alexander S. Krupnick, Melissa T. Zaidi, Daniel Kreisel, Mark H. Stoler, Amir Manafi, Oscar Okwudiri Onyema, Elizabeth A. Jacobsen, Qing Wang, Zhongcheng Mei |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Eotaxin T-Lymphocytes CD3 Receptors Antigen T-Cell Down-Regulation Mice 03 medical and health sciences 0302 clinical medicine Immune system Immune Tolerance medicine Animals Lung Mice Inbred BALB C biology Alloimmunity T-cell receptor General Medicine T lymphocyte respiratory system Eosinophil Allografts Acquired immune system Eosinophils Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Immunology biology.protein Female Research Article Lung Transplantation Signal Transduction |
| Zdroj: | JCI Insight. 4 |
| ISSN: | 2379-3708 |
| DOI: | 10.1172/jci.insight.128241 |
| Popis: | Despite the accepted notion that granulocytes play a universally destructive role in organ and tissue grafts, it has been recently described that eosinophils can facilitate immunosuppression-mediated acceptance of murine lung allografts. The mechanism of eosinophil-mediated tolerance, or their role in regulating alloimmune responses in the absence of immunosuppression, remains unknown. Using lung transplants in a fully MHC-mismatched BALB/c (H2(d)) to C57BL/6 (H2(b)) strain combination, we demonstrate that eosinophils downregulate T cell–mediated immune responses and play a tolerogenic role even in the absence of immunosuppression. We further show that such downregulation depends on PD-L1/PD-1–mediated synapse formation between eosinophils and T cells. We also demonstrate that eosinophils suppress T lymphocyte responses through the inhibition of T cell receptor/CD3 (TCR/CD3) subunit association and signal transduction in an inducible NOS–dependent manner. Increasing local eosinophil concentration, through administration of intratracheal eotaxin and IL-5, can ameliorate alloimmune responses in the lung allograft. Thus, our data indicate that eosinophil mobilization may be utilized as a novel means of lung allograft–specific immunosuppression. |
| Databáze: | OpenAIRE |
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