Type 3 innate lymphoid cells are associated with a successful intestinal transplant

Jiman Kang, Katrina Loh, Leonid Belyayev, Priscilla Cha, Mohammed Sadat, Khalid Khan, Yuriy Gusev, Krithika Bhuvaneshwar, Habtom Ressom, Sangeetha Moturi, Jason Kaiser, Jason Hawksworth, Simon C. Robson, Cal S. Matsumoto, Michael Zasloff, Thomas M. Fishbein, Alexander Kroemer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


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 NKp44ILCs (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.

Original languageEnglish
Pages (from-to)787-797
Number of pages11
JournalAmerican Journal of Transplantation
Issue number2
StatePublished - Feb 2021
Externally publishedYes


  • basic (laboratory) research/science
  • immunobiology
  • innate immunity
  • intestinal (allograft) function/dysfunction
  • intestine/multivisceral transplantation
  • ischemia-reperfusion injury (IRI)
  • mucosal immunity
  • rejection
  • translational research/science


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