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 - 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 -