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Intestinal IgA: novel views on its function in the defence of the largest mucosal surface
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  1. J MESTECKY,
  2. M W RUSSELL,
  3. C O ELSON
  1. Departments of Microbiology and Medicine,
  2. University of Alabama at Birmingham, USA
  1. Dr J Mestecky, Department of Microbiology - Box B1, 845 19th Street South, Birmingham, AL 35294–2170, USA.

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The intestine is undoubtedly the most misunderstood and under-appreciated lymphoid organ in the body. Yet, in the eyes of mucosal immunologists, the gut exemplifies finely tuned, extensively interacting populations of cells and their products involved in innate and specific defence of the body’s largest surface area, a surface exposed to the heaviest burden of environmental antigens. As the largest lymphoepithelial organ, it contains cells that absorb, process, and present antigen, B and T cells of various types, and antibody producing cells.1 Every day intestinal plasma cells produce more antibodies than do all other lymphoid organs (spleen, lymph nodes, and the bone marrow) combined.2 Although the remarkable dominance of IgA producing cells in the intestine and of IgA in the intestinal fluid has been known for decades, fine details of the migration or “homing” of IgA plasma cell precursors, their terminal differentiation, the mechanisms mediating and regulating the selective transepithelial transport of IgA, and the functional advantages of this molecule in the gut continue to emerge with impressive rapidity.

One feature unique to the mucosal immune system is the crucial role of epithelial cells of various morphological forms and phenotypes in mucosal defences.3 Functional interdependence of epithelial and lymphoid cells in the intestine has been amply documented. In addition to production of inflammatory cytokines (e.g. interleukin (IL) 8 and macrophage inflammatory protein (MIP) 1α and anti-inflammatory cytokines (e.g. transforming growth factor (TGF) β and IL-10), epithelial cells are also a source of cytokines that regulate the terminal differentiation of arriving lymphocytes into IgA producing plasma cells (e.g. TGF-β, IL-6, IL-10).3Lymphocytes resident in the lamina propria and in the intraepithelial compartment, mostly of T cell lineage, participate directly and indirectly in the protection of the mucosa,4 and provide stimuli (e.g. interferon (IFN) γ) for the maintenance …

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