Survival signal REG3α prevents crypt apoptosis to control acute gastrointestinal graft-versus-host disease.
J Clin Invest
; 128(11): 4970-4979, 2018 11 01.
Article
en En
| MEDLINE
| ID: mdl-30106382
ABSTRACT
Graft-versus-host disease (GVHD) in the gastrointestinal (GI) tract remains the major cause of morbidity and nonrelapse mortality after BM transplantation (BMT). The Paneth cell protein regenerating islet-derived 3α (REG3α) is a biomarker specific for GI GVHD. REG3α serum levels rose in the systematic circulation as GVHD progressively destroyed Paneth cells and reduced GI epithelial barrier function. Paradoxically, GVHD suppressed intestinal REG3γ (the mouse homolog of human REG3α), and the absence of REG3γ in BMT recipients intensified GVHD but did not change the composition of the microbiome. IL-22 administration restored REG3γ production and prevented apoptosis of both intestinal stem cells (ISCs) and Paneth cells, but this protection was completely abrogated in Reg3g-/- mice. In vitro, addition of REG3α reduced the apoptosis of colonic cell lines. Strategies that increase intestinal REG3α/γ to promote crypt regeneration may offer a novel, nonimmunosuppressive approach for GVHD and perhaps for other diseases involving the ISC niche, such as inflammatory bowel disease.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
1_ASSA2030
Problema de salud:
1_doencas_nao_transmissiveis
/
1_doencas_transmissiveis
Asunto principal:
Enfermedades Inflamatorias del Intestino
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Transducción de Señal
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Trasplante de Médula Ósea
/
Apoptosis
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Colon
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Células de Paneth
/
Proteínas Asociadas a Pancreatitis
/
Enfermedad Injerto contra Huésped
Tipo de estudio:
Observational_studies
/
Risk_factors_studies
Límite:
Animals
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Female
/
Humans
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Male
Idioma:
En
Revista:
J Clin Invest
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos