Loss of NLRP6 expression increases the severity of intestinal injury after syngeneic hematopoietic stem cell transplantation.

Publisher: Springer Verlag Country of Publication: Germany NLM ID: 9107334 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-0584 (Electronic) Linking ISSN: 09395555 NLM ISO Abbreviation: Ann Hematol Subsets: MEDLINE

Publication: Berlin : Springer Verlag
Original Publication: Berlin ; New York : Springer International, c1991-

Hematopoietic Stem Cell Transplantation*/adverse effects ; Mice, Inbred C57BL* ; Mice, Knockout* ; Intestinal Mucosa*/metabolism ; Intestinal Mucosa*/pathology; Animals ; Mice ; Transplantation, Isogeneic ; Apoptosis ; Intestine, Small/pathology ; Intestine, Small/metabolism ; Caspase 1/genetics ; Caspase 1/metabolism ; Caspase 1/deficiency ; Neutrophils/metabolism ; Neutrophils/pathology ; Interleukin-1beta/genetics ; Interleukin-1beta/metabolism ; CD11b Antigen/metabolism ; Pancreatitis-Associated Proteins/genetics ; Macrophages/metabolism ; Macrophages/pathology ; Receptors, Cell Surface

NLRP6 plays a crucial role in maintaining intestinal homeostasis by regulating the interaction between the intestinal mucosa and the microbiota. However, the impact of NLRP6 deficiency on intestinal damage following hematopoietic stem cell transplantation (HSCT) remains poorly understood. In this study, we established a syngeneic HSCT mouse model using C57BL/6 mice as donors and NLRP6-/- or C57BL/6 mice as recipients. Our findings revealed that NLRP6 deficiency had minimal influence on peripheral blood cell counts and splenic immune cell proportions in transplanted mice. However, it exacerbated pathological changes in the small intestine on day 14 post-transplantation, accompanied by increased proportions of macrophages, dendritic cells, and neutrophils. Furthermore, the NLRP6 deficiency resulted in elevated expression of MPO and CD11b, while reducing the levels mature caspase-1 and mature IL-1β in the intestine. Moreover, the NLRP6 deficiency disturbed the expression of apoptosis-related molecules and decreased the tight junction protein occludin. Notably, recipient mice with NLRP6 deficiency exhibited lower mRNA expression levels of antimicrobial genes, such as Reg3γ and Pla2g2a. The short-term increase in inflammatory cell infiltration caused by NLRP6 deficiency was associated with intestinal damage, increased apoptosis, reduced expression of antimicrobial peptides, and impaired intestinal repair. Taken together, our findings demonstrate that the loss of NLRP6 exacerbates post-transplantation intestinal damage in recipient mice.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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2016203007 Excellent doctoral research start-up fund of Xuzhou Medical University

Keywords: Antimicrobial peptides; Gut injury; Hematopoietic stem cell transplantation; Inflammasome; NLRP6

0 (Nod-like receptor pyrin domain-containing protein 6, mouse)
0 (Itgam protein, mouse)
EC 3.4.22.36 (Caspase 1)
0 (Interleukin-1beta)
0 (CD11b Antigen)
0 (Pancreatitis-Associated Proteins)
EC 3.4.22.36 (Casp1 protein, mouse)
0 (Receptors, Cell Surface)

Date Created: 20240412 Date Completed: 20240728 Latest Revision: 20240728

20240729

10.1007/s00277-024-05745-5

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