title: Impaired wound healing with defective expression of chemokines and recruitment of myeloid cells in TLR3-deficient mice.
abstract: Skin injury evokes both innate and adaptive immune responses to restore tissue integrity. TLRs play a critical role in host responses to injurious insults. Previous studies demonstrated that RNAs released from damaged tissues served as endogenous ligands for TLR3. In this study, we investigated the involvement of TLR3 in skin restoration after injury. Full excisional wounds were created on the skin of mice with TLR3 deficiency. We found that skin wound closure in TLR3(-/-) mice was significantly delayed compared with control littermates. Wound healing parameters, including re-epithelialization, granulation formation, and neovascularization, were decreased in TLR3(-/-) mice. Further studies revealed that the absence of TLR3 led to defective recruitment of neutrophils and macrophages, in association with decreased expression of the chemokines, MIP-2/CXCL2, MIP-1α/CCL3, and MCP-1/CCL2, in the wound. Moreover, in wild type mice, the mRNA level and protein content of TLR3 was significantly upregulated in wounded skins and silencing of TLR3 signal adaptor Toll/IL-1R domain-containing adapter inducing IFN-β with small interfering RNA retarded wound closure. These results indicate an essential role for TLR3 and Toll/IL-1R domain-containing adapter inducing IFN-β in wound healing by regulating chemokine production and recruitment of myeloid cells to wound for tissue repair.
authors.affiliation: The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lin
authors.forename: Dan
authors.initials: D
authors.lastname: Fang
authors.forename: Jiazhu
authors.initials: J
authors.lastname: Fang
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Ren
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Yang
authors.forename: Feng
authors.initials: F
authors.lastname: Wen
authors.forename: Shao Bo
authors.initials: SB
authors.lastname: Su
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000502:physiology; D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D054426:Chemokine CXCL2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D018925:Chemokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D012867:Skin / Q000276:immunology / Q000293:injuries / Q000473:pathology; D051196:Toll-Like Receptor 3 / Q000172:deficiency* / Q000502:physiology; D014945:Wound Healing / Q000235:genetics / Q000276:immunology*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D018932:Chemokine CCL2; D054426:Chemokine CXCL2; D018925:Chemokines; D051196:Toll-Like Receptor 3; C491768:Ccl2 protein, mouse; C404915:Cxcl2 protein, mouse; C476286:Ticam1 protein, mouse; C519703:TLR3 protein, mouse