Journal Article

DKFZ-2023-00580

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Epithelial Nlrp10 inflammasome mediates protection against intestinal autoinflammation.

Zheng, D. ; Mohapatra, G. ; Kern, L. ; He, Y. ; Shmueli, M. D. ; Valdés-Mas, R. ; Kolodziejczyk, A. A. ; Próchnicki, T. ; Vasconcelos, M. B. ; Schorr, L.DKFZ* ; Hertel, F.DKFZ* ; Lee, Y. S.DKFZ* ; Rufino, M. C. ; Ceddaha, E. ; Shimshy, S. ; Hodgetts, R. J. ; Dori-Bachash, M. ; Kleimeyer, C. ; Goldenberg, K. ; Heinemann, M. ; Stettner, N. ; Harmelin, A. ; Shapiro, H. ; Puschhof, J.DKFZ* ; Chen, M. ; Flavell, R. A. ; Latz, E. ; Merbl, Y. ; Abdeen, S. K. ; Elinav, E. (Last author)DKFZ*

2023
Springer Nature Limited London

Abstract: Unlike other nucleotide oligomerization domain-like receptors, Nlrp10 lacks a canonical leucine-rich repeat domain, suggesting that it is incapable of signal sensing and inflammasome formation. Here we show that mouse Nlrp10 is expressed in distal colonic intestinal epithelial cells (IECs) and modulated by the intestinal microbiome. In vitro, Nlrp10 forms an Apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC)-dependent, m-3M3FBS-activated, polyinosinic:polycytidylic acid-modulated inflammasome driving interleukin-1β and interleukin-18 secretion. In vivo, Nlrp10 signaling is dispensable during steady state but becomes functional during autoinflammation in antagonizing mucosal damage. Importantly, whole-body or conditional IEC Nlrp10 depletion leads to reduced IEC caspase-1 activation, coupled with enhanced susceptibility to dextran sodium sulfate-induced colitis, mediated by altered inflammatory and healing programs. Collectively, understanding Nlrp10 inflammasome-dependent and independent activity, regulation and possible human relevance might facilitate the development of new innate immune anti-inflammatory interventions.

Note: #LA:F220# / 2023 Apr;24(4):585-594 / #DKFZ-MOST-Ca210#

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Contributing Institute(s):

1. Mikrobiom und Krebs (F220)

Research Program(s):

1. 316 - Infektionen, Entzündung und Krebs (POF4-316) (POF4-316)

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Nature ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 30 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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