In summary, establishing novel roles for SHH and NOTCH1 signaling pathways, we found mycobacteria-activated SHH signaling induces PD-L1 and COX-2-PGE2 to mediate the expansion of CD4+CD25+FoxP3+ Tregs whereas infection-induced NOTCH1 signaling was found to suppress the Treg expansion (Fig. 8f). Here, CD4 is linked to infection.