PMID- 29550278 OWN - NLM STAT- MEDLINE DCOM- 20181221 LR - 20221207 IS - 1096-0007 (Electronic) IS - 0014-4835 (Linking) VI - 171 DP - 2018 Jun TI - TSLP-activated dendritic cells induce T helper type 2 inflammation in Aspergillus fumigatus keratitis. PG - 120-130 LID - S0014-4835(17)30796-0 [pii] LID - 10.1016/j.exer.2018.03.014 [doi] AB - Thymic stromal lymphopoietin (TSLP) is an IL-7-like cytokine, which is secreted by epithelial cells under the stimulation of Toll-like receptor (TLR) ligands. Dendritic cells (DCs) which express the thymic stromal lymphopoietin receptor (TSLPR) can be activated by TSLP. Mature DCs can express the OX40 ligand, which has the ability to combine with OX40 on the surface of T cells to stimulate T cell proliferation. TSLP secreted by corneal epithelial cells can engage in the process of T helper type 2 (Th2) inflammation in Aspergillus fumigatus keratitis, but the mechanism remains unclear. We demonstrated that in A. fumigatus-infected corneas, DCs aggregated, matured, and gradually migrated not only from the basement membrane to the corneal epithelium, but also from the corneal limbus to the central cornea. Mature DCs secreted Th2-attracting chemokines, the thymus and activation-regulated chemokine (TARC), and the macrophage-derived chemokine (MDC), encouraging the secretion of TNF-alpha and Th2 cytokine Interleukin (IL) -4, IL-5, and IL-13. The above processes were all restricted with subconjunctivally injection of TSLP siRNA, while they were strengthened with the injection of rTSLP. We demonstrated that in A. fumigatus keratitis, TSLP, through combination with TSLPR on the surface of DCs, induced DC aggregation, maturation, and migration, and then the mature DCs secreted Th2-attracting chemokines, promoting the secretion of proinflammatory cytokine TNF-alpha and Th2 cytokines, which finally induced Th2 inflammation. CI - Copyright (c) 2018 Elsevier Ltd. All rights reserved. FAU - Sun, Lin AU - Sun L AD - Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, Shandong, PR China; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health; The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, PR China. FAU - Chen, Chen AU - Chen C AD - Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, Shandong, PR China; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health; The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, PR China. FAU - Wu, Jiayin AU - Wu J AD - Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, Shandong, PR China. FAU - Dai, Chenyang AU - Dai C AD - Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, Shandong, PR China; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health; The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, PR China. FAU - Wu, Xinyi AU - Wu X AD - Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, Shandong, PR China. Electronic address: xywu8868@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180314 PL - England TA - Exp Eye Res JT - Experimental eye research JID - 0370707 RN - 0 (Chemokines) RN - 0 (Cytokines) RN - 0 (RNA, Small Interfering) RN - GT0IL38SP4 (Thymic Stromal Lymphopoietin) SB - IM MH - Animals MH - Aspergillosis/*immunology/microbiology MH - Aspergillus fumigatus MH - Blotting, Western MH - Cell Movement MH - Chemokines/metabolism MH - Corneal Ulcer/*immunology/microbiology MH - Cytokines/*physiology MH - Dendritic Cells/*immunology MH - Enzyme-Linked Immunosorbent Assay MH - Eye Infections, Fungal/*immunology/microbiology MH - Fluorescent Antibody Technique, Indirect MH - Inflammation/immunology MH - Mice MH - Mice, Inbred C57BL MH - RNA, Small Interfering/genetics MH - Real-Time Polymerase Chain Reaction MH - Th2 Cells/*immunology MH - Thymic Stromal Lymphopoietin OTO - NOTNLM OT - Aspergillus fumigatus OT - DC OT - TSLP OT - Th2 inflammation EDAT- 2018/03/20 06:00 MHDA- 2018/12/24 06:00 CRDT- 2018/03/19 06:00 PHST- 2017/11/15 00:00 [received] PHST- 2018/03/08 00:00 [revised] PHST- 2018/03/13 00:00 [accepted] PHST- 2018/03/20 06:00 [pubmed] PHST- 2018/12/24 06:00 [medline] PHST- 2018/03/19 06:00 [entrez] AID - S0014-4835(17)30796-0 [pii] AID - 10.1016/j.exer.2018.03.014 [doi] PST - ppublish SO - Exp Eye Res. 2018 Jun;171:120-130. doi: 10.1016/j.exer.2018.03.014. Epub 2018 Mar 14.