The discovery and study of inborn errors of immunity (IEI) illuminates mechanisms of human immunity and reveals candidate targets for personalized therapy. Primary immune regulatory disorders (PIRD) are a subset of IEI that present with severe autoimmunity, auto/hyperinflammation, lymphoproliferation, and/or malignancy. PIRD are treated with immunosuppressive and cytotoxic medications, often exacerbating baseline risk of severe infection, resulting in additional morbidity. Therefore, the management of PIRD must balance immune modulation and infection risk, making the understanding of the underlying mechanisms critical for optimal therapy.
Within PIRD, inflammatory bowel disease (IBD)-like phenotype constitutes the primary presentation in up to 40% of the different genetic defects. Multiple etiologies contribute to gastrointestinal (GI) pathology in IEI, including infections related to the underlying host defense impairment, immune dysregulation, and malignancy. Additionally, such processes prevalent in IEI disrupt the complex interplay between gut microbiota and the host immune system, in turn disrupting intestinal homeostasis and driving pathogenesis. Investigating the underlying mechanisms and downstream immunological consequences of IBD-like phenotypes caused by IEI allows for a precise dissection of genotype-phenotype relationship. Understanding of such relationship furthers our knowledge regarding underlying mechanisms of GI inflammatory diseases in general. Studies aimed at elucidating cellular and molecular mechanisms of currently known and novel IEI that involve GI inflammation are needed to provide additional insights into the interactions between host immunity, the microbiome, and gut function. Such studies will allow for the application of pathway specific therapy to not only particular IEIs but to GI inflammatory diseases at large, bringing precision medicine to GI pathology.
This Research Topic will give a comprehensive overview about the current understanding of IEI that present with gastrointestinal inflammation as a prominent feature of the disease, with particular emphasis on the molecular mechanisms driving pathogenesis and response to therapy. The themes addressed by this Research Topic will include, but are not limited to, the followings:
• Epithelial barrier defects that lead to mucosal inflammation.
• Phagocytic defects that lead to alterations in pathogen recognition and clearance.
• T and B cell defects that present with intestinal inflammation
• Defects in central and peripheral tolerance that lead to the disruption of intestinal homeostasis
• Disrupted gut microbiota-host interactions leading to disrupted intestinal homeostasis
Topic Editor Scott B Snapper received financial support from Pfizer and Novartis and consults for Hoffman La Roche, Amgen. Kyverna, Third Rock, Sonoma Biotherapeutics, 89bio, GentiBio and Apple Tree Life Sciences.. The other Topic Editors declare no competing interests with regard to the Research Topic subject.
The discovery and study of inborn errors of immunity (IEI) illuminates mechanisms of human immunity and reveals candidate targets for personalized therapy. Primary immune regulatory disorders (PIRD) are a subset of IEI that present with severe autoimmunity, auto/hyperinflammation, lymphoproliferation, and/or malignancy. PIRD are treated with immunosuppressive and cytotoxic medications, often exacerbating baseline risk of severe infection, resulting in additional morbidity. Therefore, the management of PIRD must balance immune modulation and infection risk, making the understanding of the underlying mechanisms critical for optimal therapy.
Within PIRD, inflammatory bowel disease (IBD)-like phenotype constitutes the primary presentation in up to 40% of the different genetic defects. Multiple etiologies contribute to gastrointestinal (GI) pathology in IEI, including infections related to the underlying host defense impairment, immune dysregulation, and malignancy. Additionally, such processes prevalent in IEI disrupt the complex interplay between gut microbiota and the host immune system, in turn disrupting intestinal homeostasis and driving pathogenesis. Investigating the underlying mechanisms and downstream immunological consequences of IBD-like phenotypes caused by IEI allows for a precise dissection of genotype-phenotype relationship. Understanding of such relationship furthers our knowledge regarding underlying mechanisms of GI inflammatory diseases in general. Studies aimed at elucidating cellular and molecular mechanisms of currently known and novel IEI that involve GI inflammation are needed to provide additional insights into the interactions between host immunity, the microbiome, and gut function. Such studies will allow for the application of pathway specific therapy to not only particular IEIs but to GI inflammatory diseases at large, bringing precision medicine to GI pathology.
This Research Topic will give a comprehensive overview about the current understanding of IEI that present with gastrointestinal inflammation as a prominent feature of the disease, with particular emphasis on the molecular mechanisms driving pathogenesis and response to therapy. The themes addressed by this Research Topic will include, but are not limited to, the followings:
• Epithelial barrier defects that lead to mucosal inflammation.
• Phagocytic defects that lead to alterations in pathogen recognition and clearance.
• T and B cell defects that present with intestinal inflammation
• Defects in central and peripheral tolerance that lead to the disruption of intestinal homeostasis
• Disrupted gut microbiota-host interactions leading to disrupted intestinal homeostasis
Topic Editor Scott B Snapper received financial support from Pfizer and Novartis and consults for Hoffman La Roche, Amgen. Kyverna, Third Rock, Sonoma Biotherapeutics, 89bio, GentiBio and Apple Tree Life Sciences.. The other Topic Editors declare no competing interests with regard to the Research Topic subject.
