Deficiency in X-linked inhibitor of apoptosis protein promotes susceptibility to microbial triggers of intestinal inflammation.
Sci Immunol
; 6(65): eabf7473, 2021 Nov 05.
Article
em En
| MEDLINE
| ID: mdl-34739342
ABSTRACT
Inflammatory bowel disease (IBD) is characterized by inappropriate immune responses to the microbiota in genetically susceptible hosts, but little is known about the pathways that link individual genetic alterations to microbiota-dependent inflammation. Here, we demonstrated that the loss of X-linked inhibitor of apoptosis protein (XIAP), a gene associated with Mendelian IBD, rendered Paneth cells sensitive to microbiota-, tumor necrosis factor (TNF), receptor-interacting protein kinase 1 (RIPK1), and RIPK3-dependent cell death. This was associated with deficiency in Paneth cellderived antimicrobial peptides and alterations in the stratification and composition of the microbiota. Loss of XIAP was not sufficient to elicit intestinal inflammation but provided susceptibility to pathobionts able to promote granulomatous ileitis, which could be prevented by administration of a Paneth cellderived antimicrobial peptide. These data reveal a pathway critical for host-microbial cross-talk, which is required for intestinal homeostasis and the prevention of inflammation and which is amenable to therapeutic targeting.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Inibidoras de Apoptose
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Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X
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Microbiota
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Inflamação
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Intestinos
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Sci Immunol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Alemanha