Hypomorphic Rag mutations in humans cause Omenn Syndrome (OS) a severe immunodeficiency associated with autoimmune-like manifestations mediated by oligoclonal activated T and B cells. The clinical and immunological spectrum of OS presentation is extremely broad. However, the role played by environmental triggers in the disease pathogenesis remains largely unknown. We have recently shown in a murine model that gut microbiota has a substantial role in determining the distinctive immune dysregulation of OS. Here, we describe how dysbiosis and loss of T cell tolerance to commensals influence the expression of autoimmunity at the barrier site and beyond, and the disease hallmark hyper-IgE. We discuss how commensal antigens and gut-derived pathogenic T cells could potentially modulate skin immunity to determine cutaneous degenerations in OS. These mechanisms may have broader implications for a deeper understanding of the role of gut microbes in influencing barriers integrity and host physiology.
RAGs and BUGS : an alliance for autoimmunity / R. Rigoni, F. Grassi, A. Villa, B. Cassani. - In: GUT MICROBES. - ISSN 1949-0976. - 7:6(2016 Nov), pp. 503-511.
|Titolo:||RAGs and BUGS : an alliance for autoimmunity|
RIGONI, ROSITA (Primo)
GRASSI, FABIO MARIA (Secondo)
|Parole Chiave:||commensal bacteria; dysbiosis; hyperIgE; IgA deficiency; immunodeficiency; RAG; T and B cell autoimmunity; Gastroenterology; Infectious Diseases; Microbiology (medical); Microbiology|
|Settore Scientifico Disciplinare:||Settore BIO/13 - Biologia Applicata|
|Data di pubblicazione:||nov-2016|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1080/19490976.2016.1228517|
|Appare nelle tipologie:||01 - Articolo su periodico|