Regulated MIP-3α/CCL20 production by human intestinal epithelium: mechanism for modulating mucosal immunity

A Izadpanah, MB Dwinell, L Eckmann… - American Journal …, 2001 - journals.physiology.org
A Izadpanah, MB Dwinell, L Eckmann, NM Varki, MF Kagnoff
American Journal of Physiology-Gastrointestinal and Liver …, 2001journals.physiology.org
Human intestinal epithelial cells secrete an array of chemokines known to signal the
trafficking of neutrophils and monocytes important in innate mucosal immunity. We
hypothesized that intestinal epithelium may also have the capacity to play a role in signaling
host adaptive immunity. The CC chemokine macrophage inflammatory protein (MIP)-
3α/CCL20 is chemotactic for immature dendritic cells and CD45RO+ T cells that are
important components of the host adaptive immune system. In these studies, we …
Human intestinal epithelial cells secrete an array of chemokines known to signal the trafficking of neutrophils and monocytes important in innate mucosal immunity. We hypothesized that intestinal epithelium may also have the capacity to play a role in signaling host adaptive immunity. The CC chemokine macrophage inflammatory protein (MIP)-3α/CCL20 is chemotactic for immature dendritic cells and CD45RO+ T cells that are important components of the host adaptive immune system. In these studies, we demonstrate the widespread production and regulated expression of MIP-3α by human intestinal epithelium. Several intestinal epithelial cell lines were shown to constitutively express MIP-3α mRNA. Moreover, MIP-3α mRNA expression and protein production were upregulated by stimulation of intestinal epithelial cells with the proinflammatory cytokines tumor necrosis factor-α or interleukin-1α or in response to infection with the enteric bacterial pathogens Salmonella or enteroinvasive Escherichia coli. In addition, MIP-3α was shown to function as a nuclear factor-κB target gene. In vitro findings were paralleled in vivo by increased expression of MIP-3α in the epithelium of cytokine-stimulated or bacteria-infected human intestinal xenografts and in the epithelium of inflamed human colon. Mucosal T cells, other mucosal mononuclear cells, and intestinal epithelial cells expressed CCR6, the cognate receptor for MIP-3α. The constitutive and regulated expression of MIP-3α by human intestinal epithelium is consistent with a role for epithelial cell-produced MIP-3α in modulating mucosal adaptive immune responses.
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