TY - JOUR
T1 - Type 3 innate lymphoid cells are associated with a successful intestinal transplant
AU - Kang, Jiman
AU - Loh, Katrina
AU - Belyayev, Leonid
AU - Cha, Priscilla
AU - Sadat, Mohammed
AU - Khan, Khalid
AU - Gusev, Yuriy
AU - Bhuvaneshwar, Krithika
AU - Ressom, Habtom
AU - Moturi, Sangeetha
AU - Kaiser, Jason
AU - Hawksworth, Jason
AU - Robson, Simon C.
AU - Matsumoto, Cal S.
AU - Zasloff, Michael
AU - Fishbein, Thomas M.
AU - Kroemer, Alexander
N1 - Funding Information:
AK, SCR, MZ, and TMF acknowledge funding support from the National Institutes of Health's National Institute of Allergy and Infectious Diseases (R01AI132389). The authors thank Valerie Bockstette for her critical review of the manuscript.
Publisher Copyright:
© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons
PY - 2021/2
Y1 - 2021/2
N2 - 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-γ) and tumor necrosis factor-alpha (TNF-α). 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.
AB - 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-γ) and tumor necrosis factor-alpha (TNF-α). 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.
KW - basic (laboratory) research/science
KW - immunobiology
KW - innate immunity
KW - intestinal (allograft) function/dysfunction
KW - intestine/multivisceral transplantation
KW - ischemia-reperfusion injury (IRI)
KW - mucosal immunity
KW - rejection
KW - translational research/science
UR - http://www.scopus.com/inward/record.url?scp=85088287721&partnerID=8YFLogxK
U2 - 10.1111/ajt.16163
DO - 10.1111/ajt.16163
M3 - Article
C2 - 32594614
AN - SCOPUS:85088287721
SN - 1600-6135
VL - 21
SP - 787
EP - 797
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 2
ER -