Yu M, Lee SM, Lee H, et al. - In this study, experts examined the expression of substance P (SP) at the ocular surface and assessed its impact on maturation of antigen presenting cells (APCs), the key cell component involved in the induction of Th17 response in dry eye disease (DED) and the influence of topical blockade of SP signaling was further examined using neurokinin-1 (NK1R) inhibitors on APC maturation, Th17 cell activation, and disease severity in a mouse model of DED. The results exhibited that at the ocular surface, SP is constitutively expressed, and in DED trigeminal ganglion (TG) neurons were the chief were source of SP. SP derived from TG improved the expression of MHC II maturation marker by BMDCs, an impact that is repudiated by blockade of SP signaling using NK1R antagonist Spantide. In conclusion, using a well-established murine model of DED, topical treatment of DED mice with NK1R antagonists CP-99,994 and L-733,060 suppressed APC acquisition of MHC II, decreased Th17 cell activity, and refined severity of the DED. These findings are of translational value, since they infer that in suppressing Th17-mediated ocular surface disease, antagonizing NK1R-mediated SP signaling could be an efficient approach.