Research Article

Endocytosis of commensal antigens by intestinal epithelial cells regulates mucosal T cell homeostasis

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Science  08 Mar 2019:
Vol. 363, Issue 6431, eaat4042
DOI: 10.1126/science.aat4042

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  • Segmented Filamentous Bacteria and immune system homeostasis
    • David K. Meyerholz, Professor of Pathology, University of Iowa Carver College of Medicine
    • Other Contributors:
      • Amanda P. Beck, Assistant Professor of Pathology, Albert Einstein College of Medicine
      • Norman F. Cheville, Emeritus Professor of Veterinary Pathology, Iowa State University

    The intestinal microbiome is recognized as an important modulator of the developing immune system. (1) Segmented Filamentous Bacteria (SFB), classified in the Clostridiaceae family of bacteria, are commonly found in the distal small intestine during early life. (2) In the ileum, SFB can adhere to absorptive epithelium (AE) on villi or preferentially to follicle associated epithelium (FAE) on Peyer’s patches. (3) Ladinsky et al. has recently shown that enterocytes use a CDC42 (cell division control protein 42 homolog) dependent mechanism for SFB antigen endocytosis that leads to Th17 cell differentiation and is important for immune system homeostasis. (4) This new pathway in enterocytes raises some stimulating questions and opportunities. 1) Host-microbe interaction: Through 16S RNA analysis of the microbe, we know that SFB display a high specificity in interactions with various species and hosts. (5, 6) As the nature of this specificity become further defined, one can envision the CDC42 pathway as an attractive target for drug delivery or even vaccinations. 2) Enterocyte location and function: Absorptive enterocytes are found in both AE and FAE, but whether the locations produce similar or site-specific variations to endocytosis pathways remains to be seen. Could the additional presence of mucous cells in the AE or M cells in the FAE modulate the enterocyte phenotype? 3) Immunosurveillance: M cells are enriched in the FAE and uptake antigens from the mucosal environment fo...

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    Competing Interests: None declared.