[Crossing between mucosal immunity and epithelial regeneration/differentiation in the human intestine]

We have demonstrated that IL-7 is produced by intestinal epithelial cells (IECs) and regulates the proliferation of IL-7R+ mucosal T cells. IEC-derived IL-7 is indispensable for both organization of mucosal lymphoid tissues and regulation of mucosal immune responses. Dysreguration of mucosal IL-7-dependent pathway leads to chronic intestinal inflammation. On the basis of the fact that IL-7R is expressed in both mucosal T cells and IECs, we found the crossing between mucosal immunity and epithelial regeneration/differentiation in human intestine. Human IECs are partly of bone marrow (BM) origin and BM-derived IECs promote the regeneration of the damaged intestinal epithelium. During regeneration following severe damage, BM-derived IECs trigger the change of IEC differentiation. BM-derived IECs mainly repopulate the absorptive IECs in normal condition, but IEC differentiation is changed toward the secretory lineage IECs during regeneration. Transcription regulation of IEC-derived IL-7 shows close relation to IEC cell specific lineage and is disturbed in chronic intestinal inflammation. Moreover, expression and function of transcription factors downstream of Notch signaling pathway that mediates IEC differentiation is changed in chronic intestinal inflammation. All these results indicated that the disorder of both IEC differentiation and mucosal immunity cause human inflammatory bowel disease.