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NKT cells and the hedgehog pathway: an unhealthy marriage in non-alcoholic fatty liver disease?
  1. Mariana Verdelho Machado,
  2. Helena Cortez-Pinto
  1. Departamento de Gastrenterologia, Unidade de Nutrição e Metabolismo, Hospital Santa Maria, Faculdade de Medicina de Lisboa, IMM, Lisbon, Portugal
  1. Correspondence to Professor Helena Cortez-Pinto, University Hospital of Santa Maria, Lisbon, Av. Prof. Egas Moniz, Lisboa 1649-028, Portugal; hlcortezpinto{at}netcabo.pt

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In the progression of non-alcoholic fatty liver disease (NAFLD) to steatohepatitis (NASH), the hedgehog (Hh) pathway has recently been implicated, with a new target gene, osteopontin (OPN), being a candidate in the coordination of inflammation and fibrosis development.1 This pathway, which is critical in embryogenesis, can be activated in adult life in the context of tissue regeneration. It has been suggested that dying and injured hepatocytes, such as ballooned hepatocytes,2 against a background of lipotoxicity, can produce Hh that will then act on inflammatory cells such as natural killer T (NKT) cells3 and on progenitor cells in such a way as to promote growth and hepatocyte differentiation, maintaining the liver mass.1 Unfortunately, it also acts on stellate cells inducing a profibrogenic phenotype.1

Syn et al4 further showed that NKT cells are responsive to Hh, and also are themselves a major source of Hh, inducing OPN production in an autocrine and paracrine fashion, thus being crucial in promoting fibrogenesis in NASH. The authors evaluated wild-type and knockout mice with NKT cell depletion, either knockout for the specific junction J α …

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