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Soriano Romani, Laura Contreras Ruiz, Laura López García, Antonio Diebold Luque, María Yolanda Masli, Sharmila 2022-03-08T13:45:03Z 2022-03-08T13:45:03Z 2019 International Journal of Molecular Sciences, 2019, vol. 20, n. 1, p. 9. 1661-6596 https://uvadoc.uva.es/handle/10324/52280 10.3390/ijms20010009 9 1 International Journal of Molecular Sciences 20 1422-0067 Producción Científica Chronic inflammation of the ocular surface poses a risk of vision impairment. The understanding of the molecular mechanisms that are involved in the inflammatory response is critical to identify novel molecular targets. Recently, thrombospondin-1 (TSP-1) has emerged as a key player in ocular surface homeostasis that efficiently activates the TGF-β2 isoform that is predominantly expressed in the ocular mucosa. Here, the potential of the peptide derived from TSP-1 (KRFK), that can activate TGF-β, is proposed as a potentially applicable therapeutic for chronic ocular surface inflammatory disorders. Our in vitro results confirm that the chosen peptide activates TGF-β, reducing the expression of co-stimulatory molecules on dendritic cells, driving them towards a tolerogenic phenotype. For the in vivo studies, the TSP-1−/− mouse is used as a pre-clinical model of chronic ocular inflammation. We observe that the topical application of KRFK alters the peripheral balance of effectors by reducing the proportion of pathogenic Th1 and Th17 cells while increasing Treg cell proportion in cervical lymph nodes. In line with these findings, the development of chronic ocular surface inflammation is significantly prevented in KRFK-treated TSP-1−/− mice, as assessed by clinical parameters and inflammatory cytokine expression in conjunctival and lacrimal gland tissues. Together, our results identify the KRFK peptide as a novel therapeutic option to prevent the development of chronic inflammatory manifestations of the ocular surface. Ministerio de Economía, Industria y Competitividad (FEDER-CICYT grant MAT2013-47501-C02-1-R) Massachusetts Lions Eye Research Fund (MLERF, S.M.) and NEI grant EY015472 (S.M.) Junta de Castilla y León - Fondo Social Europeo (project VA098-12) application/pdf eng MDPI info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/4.0/ © 2018 The Authors Atribución 4.0 Internacional Inflammation KRFK peptide Ocular surface Thrombospondin-1 Transforming growth factor-β 32 Ciencias Médicas Topical application of TGF-β-activating peptide, KRFK, prevents inflammatory manifestations in the TSP-1-deficient mouse model of chronic ocular inflammation info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion https://www.mdpi.com/1422-0067/20/1/9 SI