A potential link between TSLP/TSLPR/STAT5 and TLR2/MyD88/NFκB-p65 in human corneal epithelial cells for Aspergillus fumigatus tolerance

Publication date: March 2016 Source:Molecular Immunology, Volume 71 Author(s): Xiaoxiao Ren, Leyi Wang, Xinyi Wu 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. To further confirm the role of TSLP/TSLPR/STAT5 signaling pathway in HCECs, before incubated HCECs with A. fumigatus hyphae we inhibited STAT5 activity by STAT5 siRNA transfection and then detected IL-13 by ELISA. STAT5 knockdown attenuated the release of IL-13 triggered by A. fumigatus hyphae.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 downst...
Source: Molecular Immunology - Category: Allergy & Immunology Source Type: research