Non-alcoholic fatty liver disease (NAFLD) is becoming one of the most common chronic liver diseases worldwide. Although NAFLD is in part secondary to the western lifestyle, recent evidence suggests that intrinsic mechanisms can contribute to the development of NAFLD and progression to its more aggressive form of steatohepatitis. Many of the main molecular and immunological mechanisms suggested as responsible for the development of an inflammatory disorder in NAFLD and non-alcoholic steatohepatitis (NASH) are shared with immune-mediated inflammatory diseases (IMID), such as inflammatory bowel disease and psoriasis, among others. These mechanisms include, for instance, the inflammatory pathways depending on TNF-alpha, toll-like receptor (TLR) signalling, or inflammasome activity; the imbalance in T-cell subtypes like Th17/Treg; the disregulation of myeloid-derived suppressor cells or innate lymphoid cells; and the involvement of both membrane-bound and soluble immune checkpoint pathways able to stimulate or suppress immune cell functions. This common pathogenesis may explain, at least in a subset of patients, the development of NASH in the absence of classic metabolic risk factors. In this way, NASH could be considered as an IMID, as most of the defining features of IMID are present. The “second hit” hypothesis proposes the triggering effect of different stimuli that could induce these diseases and could influence the NAFLD and NASH progression. These stimuli include metabolic and non-metabolic factors as well as bioactive substances from the gut microbiome. As an IMID, immune parameters could be useful in the clinical diagnosis and prognosis definition of NAFLD and NASH. Furthermore, immune intervention in this emergent IMID disease might be applicable.
This Research Topic is aimed at collecting recent evidence from basic and translational research on the possible link between NAFLD/NASH and IMID, with a focus on the role of innate immunity, including TLR signalling and the induction of inflammatory responses, in the onset of NAFLD and its progression to NASH. How the inflammatory response can establish a mechanistic link between NAFLD and any other IMID is of particular interest.
We welcome the submission of Original Research, Review, Mini-Reviews and Clinical Trial articles that include, but are not limited to, the following subtopics:
• Immune mechanisms in the pathogenesis of NAFLD/NASH
• The role of intestinal myeloid-derived suppressor cells (MDSCs) in promoting NAFLD/NASH
• Inflammatory spectrum of NAFLD/NASH
• Association between NAFLD and IMID
• Immunological laboratory marker for diagnosis of NAFLD
• “Second hit” in NAFLD and NASH progression (metabolic syndrome, immunoregulation, microbiome etc.)
• Definition of immunological prognostic factors in NAFLD/NASH
• Immune therapy options
Non-alcoholic fatty liver disease (NAFLD) is becoming one of the most common chronic liver diseases worldwide. Although NAFLD is in part secondary to the western lifestyle, recent evidence suggests that intrinsic mechanisms can contribute to the development of NAFLD and progression to its more aggressive form of steatohepatitis. Many of the main molecular and immunological mechanisms suggested as responsible for the development of an inflammatory disorder in NAFLD and non-alcoholic steatohepatitis (NASH) are shared with immune-mediated inflammatory diseases (IMID), such as inflammatory bowel disease and psoriasis, among others. These mechanisms include, for instance, the inflammatory pathways depending on TNF-alpha, toll-like receptor (TLR) signalling, or inflammasome activity; the imbalance in T-cell subtypes like Th17/Treg; the disregulation of myeloid-derived suppressor cells or innate lymphoid cells; and the involvement of both membrane-bound and soluble immune checkpoint pathways able to stimulate or suppress immune cell functions. This common pathogenesis may explain, at least in a subset of patients, the development of NASH in the absence of classic metabolic risk factors. In this way, NASH could be considered as an IMID, as most of the defining features of IMID are present. The “second hit” hypothesis proposes the triggering effect of different stimuli that could induce these diseases and could influence the NAFLD and NASH progression. These stimuli include metabolic and non-metabolic factors as well as bioactive substances from the gut microbiome. As an IMID, immune parameters could be useful in the clinical diagnosis and prognosis definition of NAFLD and NASH. Furthermore, immune intervention in this emergent IMID disease might be applicable.
This Research Topic is aimed at collecting recent evidence from basic and translational research on the possible link between NAFLD/NASH and IMID, with a focus on the role of innate immunity, including TLR signalling and the induction of inflammatory responses, in the onset of NAFLD and its progression to NASH. How the inflammatory response can establish a mechanistic link between NAFLD and any other IMID is of particular interest.
We welcome the submission of Original Research, Review, Mini-Reviews and Clinical Trial articles that include, but are not limited to, the following subtopics:
• Immune mechanisms in the pathogenesis of NAFLD/NASH
• The role of intestinal myeloid-derived suppressor cells (MDSCs) in promoting NAFLD/NASH
• Inflammatory spectrum of NAFLD/NASH
• Association between NAFLD and IMID
• Immunological laboratory marker for diagnosis of NAFLD
• “Second hit” in NAFLD and NASH progression (metabolic syndrome, immunoregulation, microbiome etc.)
• Definition of immunological prognostic factors in NAFLD/NASH
• Immune therapy options
