@article {1532368,
	title = {Restoration of Regulatory T-Cell Function in Dry Eye Disease by Antagonizing Substance P/Neurokinin-1 Receptor},
	journal = {Am J Pathol},
	volume = {190},
	number = {9},
	year = {2020},
	month = {2020 09},
	pages = {1859-1866},
	abstract = {Substance P (SP) is a tachykinin neuropeptide, implicated in the pathogenesis of various inflammatory conditions and a critical mediator in pain transmission. Recently, the role of SP was described in the pathogenesis of dry eye disease (DED) through its role in the maturation of antigen-presenting cells at the ocular surface after exposure to desiccating stress. However, the effect of SP on regulatory T cells (Tregs), which are functionally impaired in DED, remains unclear. This study examined the phenotypic and functional changes in Tregs in response to SP in DED. The in\&nbsp;vitro cultures of normal Tregs in the presence of SP led to a significant reduction in both Treg frequencies and their suppressive function, which was prevented by the addition of an SP receptor (neurokinin-1 receptor) antagonist. Furthermore, in\&nbsp;vivo treatment with the neurokinin-1 receptor antagonist in DED mice effectively restored Treg function, suppressed pathogenic T helper 17 response, and significantly ameliorated the disease. Our results show that a significant increase in SP levels promotes Treg dysfunction in DED, and blockade of SP effectively restores Treg function and suppresses DED severity.},
	keywords = {Animals, Dry Eye Syndromes, Female, Mice, Mice, Inbred C57BL, Neurokinin-1 Receptor Antagonists, Receptors, Neurokinin-1, T-Lymphocytes, Regulatory},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2020.05.011},
	author = {Taketani, Yukako and Marmalidou, Anna and Dohlman, Thomas H and Singh, Rohan Bir and Amouzegar, Afsaneh and Chauhan, Sunil K and Chen, Yihe and Dana, Reza}
}
