Abnormal CX3CR1 + lamina propria myeloid cells from intestinal transplant recipients with NOD2 mutations

D. Lough, J. Abdo, J. F. Guerra-Castro, C. Matsumoto, S. Kaufman, K. Shetty, Y. K. Kwon, M. Zasloff, Thomas M. Fishbein

Research output: Contribution to journalArticle

Abstract

Although progress has been made in intestinal transplantation, chronic inflammation remains a challenge. We have reported that the risk of immunological graft loss is almost 100-fold greater in recipients who carry any of the prevalent NOD2 polymorphisms associated with Crohn's disease, and have shown that the normal levels of a key antimicrobial peptide produced by the Paneth cells of the allograft, fall as the graft becomes repopulated by hematopoietic cells of the NOD2 mutant recipient. These studies are extended in this report. Within several months following engraftment into a NOD2 mutant recipient the allograft loses its capacity to prevent adherence of lumenal microbes. Despite the significantly increased expression of CX3CL1, a stress protein produced by the injured enterocyte, NOD2 mutant CX3CR1 + myeloid cells within the lamina propria fail to exhibit the characteristic morphological phenotype, and fail to express key genes required expressed by NOD2 wild-type cells, including Wnt 5a. We propose that the CX3CR1 + myeloid cell within the lamina propria supports normal Paneth cell function through expression of Wnt 5a, and that this function is impaired in the setting of intestinal transplantation into a NOD2 mutant recipient. The therapeutic value of Wnt 5a administration in this setting is proposed.

Original languageEnglish (US)
Pages (from-to)992-1003
Number of pages12
JournalAmerican Journal of Transplantation
Volume12
Issue number4
DOIs
Publication statusPublished - Apr 2012
Externally publishedYes

    Fingerprint

Keywords

  • Human defensin 5
  • Intestinal transplant
  • NOD 2
  • Paneth cell
  • Wnt 5a

ASJC Scopus subject areas

  • Transplantation
  • Immunology and Allergy
  • Pharmacology (medical)

Cite this

Lough, D., Abdo, J., Guerra-Castro, J. F., Matsumoto, C., Kaufman, S., Shetty, K., ... Fishbein, T. M. (2012). Abnormal CX3CR1 + lamina propria myeloid cells from intestinal transplant recipients with NOD2 mutations. American Journal of Transplantation, 12(4), 992-1003. https://doi.org/10.1111/j.1600-6143.2011.03897.x