We found that TLR2-dependent signaling in IECs played an important role in development of IELs (especially CD8αα+TCRαβ+ and TCRγδ+ IELs), and the signaling was essential in transcriptional activation of IL-15 via NK-κB. Furthermore, we have shown that loss of IELs contributes to the high susceptibility of TLR2−/− mice to DSS-induced colitis. The gene discussed is IL15; the disease is colitis.