Although it has been previously demonstrated that MSCs directly regulate the proliferation and differentiation of CD4+ T cells in vitro [53], which cannot well reproduce the real interaction between MSCs and host in vivo due to the existence of the complicated physiological process influenced by various factors, as indicated by our results that the effect on restoring Treg/Th2/Th17 balance by HUMSCs in colitis disappeared following gut microbiota depletion. The gene discussed is CD4; the disease is colitis.