A. Infectious complications are the leading cause of death early after intestinal transplantation (ITx). Etiologies underlying this remain unclear. Innate lymphoid cells (ILCs) have very recently been shown to be key regulators of epithelial homeostasis and antimicrobial defense. Since ILC function in ITx is completely unknown, we tested the hypothesis that ILCs play a key regulatory role after ITx by controlling the host-microbial interface.

B. Intestinal biopsies (bx) were obtained after recent ITx and followed longitudinally. Phenotypic analysis of cells was conducted by polychromatic flow cytometry and IHC. Graft infiltrating lymphocytes were flow sorted and rtPCR was performed to investigate effector cytokine and transcription factor profiles.

C. First, we calculated the incidence of gram negative rod (GNR) bacteremia in the 6 month period following ITx. In the last 5 years, early post-op GNR bacteremia occurred in 31% of 85 ITx recipients. Given the essential role of ILCs in antimicrobial defense, we hypothesized that the pathogenesis of GNR bacteremia and translocation after ITx is due to ILC dysregulation. To test this hypothesis we studied serial ITx bxs longitudinally from the day of Tx via flow cytometry and IHC. Surprisingly, we found almost complete absence of protective ILC subsets in all recipients as early as 4h reperfusion compared to healthy ITx recipients at least 6 months following ITx (0.145% v 4.96%, p<0.001). Importantly, further subset analyses via flow cytometry and rtPCR of flow-sorted ILCs in the healthy cohort revealed that protective ILC subsets were present as shown by expression of NKp44, CD117, CD127 and CCR6. Further mRNA transcription profile studies revealed expression of the hallmark transcription factor RORγt, as well as the signature cytokine IL-22, both of which have been shown to play key roles in antimicrobial defense. These findings suggest that dysregulation of protective ILC populations in the immediate post-op period contributes to infectious complications secondary to attenuated antimicrobial defenses.

D. This study shows that the ILC population immediately following ITx is dysregulated and regenerates over time. The study also shows that ILC dysregulation after ITx plays a role in the pathogenesis of infectious complications, which previously unknown, may be of high clinical relevance.

CITATION INFORMATION: Kaiser J, Cosentino C, Shukla A, Desai C, Girlanda R, Hawksworth J, Matsumoto C, Zasloff M, Fishbein T, Kroemer A. Innate Lymphoid Cells Play a Key Role in Controlling Antimicrobial Defense in Intestinal Transplant Recipients. Am J Transplant. 2016;16 (suppl 3).

« Back to 2016 American Transplant Congress