PMID- 37607465 OWN - NLM STAT- Publisher LR - 20231017 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 124 IP - Pt A DP - 2023 Nov TI - Chitinase 3-like 1 plays a pivotal role in airway response of RSV infection via regulating DC functional transition. PG - 110819 LID - S1567-5769(23)01144-X [pii] LID - 10.1016/j.intimp.2023.110819 [doi] AB - BACKGROUND: Dendritic cells (DCs) contribute to immune imbalance and airway hyperresponsiveness (AHR) induced by respiratory syncytial virus (RSV). The aim of present study was to explore the mechanism of RSV regulating naive T cell differentiation through DCs. METHODS: We generated a Lentivirus shRNA expression vector to knock down CHI3L1 in mouse lungs and bone marrow-derived dendritic cells (BMDCs). Then we investigated the effect of CHI3L1 knockdown on MAPK/ERK pathway, PI3K/AKT pathway, mature DCs represented by molecular markers, naive T cell differentiation and related cytokine expression in vitro and in vivo models of RSV. RESULTS: RSV elevated CHI3L1 expression in lung DCs and BMDCs. Knockdown of CHI3L1 impeded RSV-induced activation of MAPK/ERK and PI3K/AKT signaling pathways, attenuated CD86 and OX40L expression in mature DCs, reduced the proportion of Th2 and Th17 cells, and increased the proportion of Treg cells. In addition, by blocking CHI3L1, RSV-infected mice shown relief of airway resistance, the downregulation of Th2/Th17 like cytokines IL-4, IL-13 and IL-17 levels, and the upregulation of IL-10. CONCLUSION: Our data show that CHI3L1 promotes RSV induced immune imbalance and airway hyperresponsiveness by regulating the functional transformation of DCs. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Ge, Lingli AU - Ge L AD - Department of Pediatrics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China; Department of Pediatrics, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, China. Electronic address: gelingli0505@163.com. FAU - Wang, Yuxin AU - Wang Y AD - Department of Pediatrics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China. Electronic address: 751026394@qq.com. FAU - Liu, Zhi AU - Liu Z AD - Department of Pediatrics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China. Electronic address: 83972576@qq.com. FAU - Du, Hui AU - Du H AD - Department of Pediatrics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China. Electronic address: 13407180763@163.com. FAU - Zhao, Dongchi AU - Zhao D AD - Department of Pediatrics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China; Children's digital health and data Center of Wuhan University, Wuhan, Hubei, China. Electronic address: zhao_wh2004@hotmail.com. LA - eng PT - Journal Article DEP - 20230820 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 SB - IM OTO - NOTNLM OT - Chitinase 3-like 1 OT - Immune response OT - Immunogenic maturation OT - Lung dendritic cells OT - Respiratory syncytial virus OT - T lymphocytes COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/08/23 00:41 MHDA- 2023/08/23 00:41 CRDT- 2023/08/22 18:06 PHST- 2023/06/11 00:00 [received] PHST- 2023/08/11 00:00 [revised] PHST- 2023/08/16 00:00 [accepted] PHST- 2023/08/23 00:41 [pubmed] PHST- 2023/08/23 00:41 [medline] PHST- 2023/08/22 18:06 [entrez] AID - S1567-5769(23)01144-X [pii] AID - 10.1016/j.intimp.2023.110819 [doi] PST - ppublish SO - Int Immunopharmacol. 2023 Nov;124(Pt A):110819. doi: 10.1016/j.intimp.2023.110819. Epub 2023 Aug 20.