GVHD, IBD, and primary immunodeficiencies: The gut as a target of immunopathology resulting from impaired immunity.

The intestinal tract is the largest immunological organ in the body and has a central function of regulating local immune responses, as the intestinal epithelial barrier is a location where the immune system interacts with the gut microbiome including bacteria, fungi, and viruses. Impaired immunity in the intestinal tract can lead to immunopathology, which manifests in different diseases such as inflammatory bowel disease or intestinal graft-versus-host disease. A disturbed communication between epithelial cells, immune cells, and microbiome will shape pathogenic immune responses to antigens, which need to be counterbalanced by tolerogenic mechanisms and repair mechanisms. Here, we review how impaired intestinal immune function leads to immunopathology with a specific focus on innate immune cells, the role of the microbiome, and the resulting clinical manifestations including intestinal graft-versus-host disease, inflammatory bowel disease, and enteropathy in primary immunodeficiency.