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J Pediatr Gastroenterol Nutr ; 74(6): 742-749, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35258491

RESUMO

OBJECTIVES: The activation of innate immune mechanisms is key for chronic liver injury. Interleukin-37 (IL-37) is a profound inhibitor of innate and adaptive immune responses, and its overexpression protects mice from liver inflammation and fibrosis. Here, we characterize the hepatic inflammatory infiltrate and expression of IL-37 in children with autoimmune liver diseases. METHODS: We compared the inflammatory microenvironment of the liver in a retrospective cohort of children with primary sclerosing cholangitis (PSC), autoimmune sclerosing cholangitis (ASC) and autoimmune hepatitis (AIH) by immunohistochemistry. The expression of IL-37 was quantified in liver parenchyma and portal tracts. Double immunofluorescence was used for detection of IL-37 in specific cell types and colocalization with Smad3. RESULTS: AIH is characterized by a dense lymphoplasmacytic infiltrate whereas ASC shows high numbers of granulocytes in portal tracts. IL-37 expression correlates positively with liver inflammation and fibrosis, the number of infiltrating immune cells and serum markers for hepatic inflammation. IL-37 is mainly expressed in hepatocytes, cholangiocytes and infiltrating immune cells. Double staining revealed IL-37 positivity in T helper and regulatory T cells (Treg), Kupffer (KC) and hepatic stellate cells (HSC). IL-37 colocalizes with intranuclear pSmad3L in areas of liver inflammation. CONCLUSIONS: Pediatric ASC separates from PSC and AIH by a granulocyte-rich portal infiltrate. Upregulation of IL-37 with liver injury, the expression in Treg as well as KC and HSC and the colocalization of IL-37 with pSmad3L in cholangiocytes and hepatocytes suggest a modulating role to limit hepatic inflammation and fibrosis in pediatric autoimmune liver diseases.


Assuntos
Doenças Autoimunes , Colangite Esclerosante , Hepatite Autoimune , Hepatopatias , Animais , Colangite Esclerosante/patologia , Fibrose , Hepatite Autoimune/patologia , Humanos , Inflamação/patologia , Fígado/patologia , Cirrose Hepática/patologia , Hepatopatias/patologia , Camundongos , Estudos Retrospectivos
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