Type 3 innate lymphoid cells are associated with a successful intestinal transplant.
Citation: American Journal of Transplantation. 21(2):787-797, 2021 02.PMID: 32594614Institution: MedStar Health Research Institute | MedStar Washington Hospital CenterDepartment: MedStar General Surgery ResidencyForm of publication: Journal ArticleMedline article type(s): Journal Article | Research Support, N.I.H., ExtramuralSubject headings: IN PROCESS -- NOT YET INDEXEDYear: 2021ISSN:- 1600-6135
- Kroemer, Alexander:
- https://orcid.org/0000-0002-9842-4973
Item type | Current library | Collection | Call number | Status | Date due | Barcode |
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Journal Article | MedStar Authors Catalog | Article | 32594614 | Available | 32594614 |
Although innate lymphoid cells (ILCs) play fundamental roles in mucosal barrier functionality and tissue homeostasis, ILC-related mechanisms underlying intestinal barrier function, homeostatic regulation, and graft rejection in intestinal transplantation (ITx) patients have yet to be thoroughly defined. We found protective type 3 NKp44+ ILCs (ILC3s) to be significantly diminished in newly transplanted allografts, compared to allografts at 6 months, whereas proinflammatory type 1 NKp44- ILCs (ILC1s) were higher. Moreover, serial immunomonitoring revealed that in healthy allografts, protective ILC3s repopulate by 2-4 weeks postoperatively, but in rejecting allografts they remain diminished. Intracellular cytokine staining confirmed that NKp44+ ILC3 produced protective interleukin-22 (IL-22), whereas ILC1s produced proinflammatory interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). Our findings about the paucity of protective ILC3s immediately following transplant and their repopulation in healthy allografts during the first month following transplant were confirmed by RNA-sequencing analyses of serial ITx biopsies. Overall, our findings show that ILCs may play a key role in regulating ITx graft homeostasis and could serve as sentinels for early recognition of allograft rejection and be targets for future therapies. Copyright (c) 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.
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