Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells

Nature Immunology  6, 507-514 (2005)

Speaker：吳得嘉                       Time：14:00~15:00, March 1 , 2006

Commentator：謝奇璋 醫師              Place：Room 601

Abstract :

Dendritic cells (DC) in intestinal mucosa can actively send their dendrites out of the mucosal epithelial cells which provide the first line of defense of microorganisms entry. These DCs sample not only invasive pathogens but also commensal bacteria to induce further immune responses. Pathogens and commensal bacteria share many structures recognized by Toll-like receptors which control many immune signals, however, it is unclear how exaggerated inflammatory responses to bacteria flora. In order to prevent the dysregulated immune responses to food or commensal bacteria, the gut-associated DCs are more prone to induce tolerogenic immunity. The authors hypothesized that the mucosal environment such as epithelial cells which are in close contact with DCs educates DCs to mount default noninflammatory responses to preserve gut immune homeostasis, rather than it is due to any special intrinsic factors in mucosal DCs. First of all, the authors purified human colon DCs and confirmed that these DCs promote Th2 polarization and reduce IL-12 production. Because previous studies showed that thymic stromal lymphopoietin (TSLP)-activated DCs can induce the differentiation of Th2 cells, the authors detected whether epithelial cells can release TSLP. The results demonstrated that TSLP will be constitutively released by epithelial cells and induce upregulation of the TSLP receptors expression in DCs. Caco-2 cells (human colon cell line) supernatant which contains TSLP concentration in a narrow window (0.07~0.15ng/ml) can promote Th2 polarization and reduce IL-12 and IFN-γ production to inhibit immune activation. When invasive pathogens are added, the TSLP production will be out of the concentration window. The T cells will polarize toward Th1 and induce inflammatory response to clear pathogen. Finally, the authors have shown that deregulation of TSLP expression could be crucial in the establishment of intestinal inflammatory bowel disease. In conclusion, the results suggest the existence of a default mechanism mediated by TSLP released constitutively by ECs that helps maintain the homeostasis of the gut by generating a noninflammatory environment.

References :

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