title: A potential link between TSLP/TSLPR/STAT5 and TLR2/MyD88/NFκB-p65 in human corneal epithelial cells for Aspergillus fumigatus tolerance.
abstract: Our previous studies reported that pattern recognition receptors (PRRs), including the cell surface Toll-like receptors (TLRs) and cytoplasmic NOD-like receptors (NLRs), recognize pathogen-associated molecular patterns (PAMPS) to initiate downstream signal cascades to active immunity responses. Thymic stromal lymphopoietin (TSLP) has recently emerged as a key cytokine in the development of type 2 adaptive immune responses. However, the crosstalk between PRRs and TSLP has not been well elucidated in Aspergillus fumigates keratitis. Our studies demonstrated that HCECs not only respond to TSLP, but also initiate immunological regulation through TSLP/TSLPR/STAT5 signaling pathway. In addition, we revealed that zymosan TLR2 agonist enhanced the expression of TSLP and TSLPR and phosphorylation of STAT5. Furthermore, neutralization of TLR2 with monoclonal Ab prevented the production of TSLP and TSLPR and phosphorylation of STAT5 from increasing which induced by A. fumigatus hyphae. Interestingly, we also found that human recombinant TSLP induced the increase of TLR2 downstream signal molecules, and TSLP knockdown could reduce the increase of TLR2 downstream signaling molecules(MyD88 and NF-κB-p65) induced by A. fumigatus hyphae. These studies indicated that HCECs represent a novel target of TSLP, TSLP/TSLPR/STAT5 signaling plays an important role in response to A. fumigatus infection in HCECs, and TLR2 downstream signaling molecules up regulate TSLP/TSLPR/STAT5 signaling as well as TSLP downstream signaling molecules up regulate TLR2/MyD88/NFκB-p65 signaling in this phenomenon.
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Shandong University, Jinan, Shandong, People's Republic of China; Department of Ophthalmology, Qilu Hospital of Shandong University, Wenhua Xi Road 107, Jinan, Shandong, People's Republic of China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Ren
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Shandong University, Jinan, Shandong, People's Republic of China; Department of Ophthalmology, Qilu Hospital of Shandong University, Wenhua Xi Road 107, Jinan, Shandong, People's Republic of China.
authors.forename: Leyi
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Qilu Hospital of Shandong University, Wenhua Xi Road 107, Jinan, Shandong, People's Republic of China. Electronic address: xywu8868@163.com.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Wu
mesh_terms: D001228:Aspergillosis / Q000276:immunology*; D001232:Aspergillus fumigatus; D015153:Blotting, Western; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D019573:Epithelium, Corneal / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007634:Keratitis / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D018121:Receptors, Cytokine / Q000276:immunology; D050799:STAT5 Transcription Factor / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology; D051996:Transcription Factor RelA / Q000276:immunology; D000094632:Thymic Stromal Lymphopoietin
chemical_list: C498762:CRLF2 protein, human; D016207:Cytokines; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D018121:Receptors, Cytokine; D050799:STAT5 Transcription Factor; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051996:Transcription Factor RelA; D000094632:Thymic Stromal Lymphopoietin
keywords: HCECs; STAT5; TLR2; TSLPR