title: Altered expression of lymphocyte homing chemokines in the pathogenesis of IgA nephropathy.
abstract: Defective adaptive humoral immune responses to mucosal immunogens, but intact systemic responses, are increasingly recognized in patients with IgA nephropathy (IgAN). Reduced expression of IgA+, J chain+ cells in the gut lamina propria, with collateral increases in these cells in the marrow, is also documented. Thus, there seems to be a derangement in a 'mucosa-marrow axis' in IgAN patients. Recent evidence indicates that chemokines regulate the localization of B cells and their progeny into respiratory and intestinal lamina propria, and into other lymphoid organs as well. Particularly, secretory epithelial cells express the chemokine CCL28, whereas small bowel cells uniquely express CCL25. Extramucosal sites preferentially express CXCL12, CXCL13 and/or CXCL16. Reciprocally, plasmablasts committed to IgA synthesis ubiquitously express the receptor (CCR10) for CCL28, and a subset also express the receptor (CCR9) for CCL25; neither of these is present on cells committed to IgG or IgM synthesis. Herein, the potential contributions of virally induced innate responses to defective mucosal immunity and overproduction of oligomeric IgA in the marrow and tonsils will be reviewed, particularly with respect to the influence that viral infection exerts upon the expression of selected chemokine and receptor pairs. The ramifications for pathogenesis of IgAN will be considered.
authors.affiliation: Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Buren
authors.forename: Michifumi
authors.initials: M
authors.lastname: Yamashita
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tomino
authors.forename: Steven N
authors.initials: SN
authors.lastname: Emancipator
mesh_terms: D018925:Chemokines / Q000276:immunology*; D005922:Glomerulonephritis, IGA / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology*; D019707:Receptors, Chemokine / Q000276:immunology*
chemical_list: D018925:Chemokines; D019707:Receptors, Chemokine