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A potential link between TSLP/TSLPR/STAT5 and TLR2/MyD88/NFκB-p65 in human corneal epithelial cells for Aspergillus fumigatus tolerance.
Mol Immunol 2016; 71:98-106MI

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+Show Affiliations

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.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.Department of Ophthalmology, Qilu Hospital of Shandong University, Wenhua Xi Road 107, Jinan, Shandong, People's Republic of China. Electronic address: xywu8868@163.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26874828

Citation

Ren, Xiaoxiao, et al. "A Potential Link Between TSLP/TSLPR/STAT5 and TLR2/MyD88/NFκB-p65 in Human Corneal Epithelial Cells for Aspergillus Fumigatus Tolerance." Molecular Immunology, vol. 71, 2016, pp. 98-106.
Ren X, Wang L, Wu X. A potential link between TSLP/TSLPR/STAT5 and TLR2/MyD88/NFκB-p65 in human corneal epithelial cells for Aspergillus fumigatus tolerance. Mol Immunol. 2016;71:98-106.
Ren, X., Wang, L., & Wu, X. (2016). A potential link between TSLP/TSLPR/STAT5 and TLR2/MyD88/NFκB-p65 in human corneal epithelial cells for Aspergillus fumigatus tolerance. Molecular Immunology, 71, pp. 98-106. doi:10.1016/j.molimm.2015.12.014.
Ren X, Wang L, Wu X. A Potential Link Between TSLP/TSLPR/STAT5 and TLR2/MyD88/NFκB-p65 in Human Corneal Epithelial Cells for Aspergillus Fumigatus Tolerance. Mol Immunol. 2016;71:98-106. PubMed PMID: 26874828.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A potential link between TSLP/TSLPR/STAT5 and TLR2/MyD88/NFκB-p65 in human corneal epithelial cells for Aspergillus fumigatus tolerance. AU - Ren,Xiaoxiao, AU - Wang,Leyi, AU - Wu,Xinyi, Y1 - 2016/02/11/ PY - 2015/10/22/received PY - 2015/12/14/revised PY - 2015/12/23/accepted PY - 2016/2/15/entrez PY - 2016/2/15/pubmed PY - 2016/8/3/medline KW - HCECs KW - STAT5 KW - TLR2 KW - TSLPR SP - 98 EP - 106 JF - Molecular immunology JO - Mol. Immunol. VL - 71 N2 - 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. SN - 1872-9142 UR - https://www.unboundmedicine.com/medline/citation/26874828/A_potential_link_between_TSLP/TSLPR/STAT5_and_TLR2/MyD88/NFκB_p65_in_human_corneal_epithelial_cells_for_Aspergillus_fumigatus_tolerance_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0161-5890(15)30136-X DB - PRIME DP - Unbound Medicine ER -