PMID- 37611690 OWN - NLM STAT- MEDLINE DCOM- 20231115 LR - 20231122 IS - 1879-0003 (Electronic) IS - 0141-8130 (Linking) VI - 252 DP - 2023 Dec 1 TI - Actinidia eriantha polysaccharide exerts adjuvant activity by targeting linc-AAM. PG - 126440 LID - S0141-8130(23)03336-6 [pii] LID - 10.1016/j.ijbiomac.2023.126440 [doi] AB - Actinidia eriantha polysaccharide (AEPS) is a potent adjuvant with dual Th1 and Th2 potentiating activity. linc-AAM has been previously proved to facilitate the expression of immune response genes (IRGs) in AEPS-activated RAW264.7 macrophages. However, its role in mediating adjuvant activity of AEPS remains to be elucidated. In this study, bone marrow-derived macrophages (BMDMs) from wide-type (WT) and linc-AAM knockout C57BL/6J mice treated with AEPS were subjected to transcriptome sequencing and bioinformatic analysis. linc-AAM deficiency inhibited M1 and M2 immune responses in BMDMs induced by AEPS. In mechanisms, AEPS facilitated the expression of IRGs and activated BMDMs through NF-kappaB-linc-AAM-JAK/STAT axis. Furthermore, linc-AAM knockout inhibited cytokine and chemokine production, immune cell recruitment as well as immune cell migration to draining lymph nodes at peritoneal cavity in mice induced by AEPS. More importantly, linc-AAM deletion reduced the adjuvant activity of APES on antigen-specific cellular and humoral immune responses to ovalbumin in mice. This study has for the first time demonstrated the role of lncRNAs in regulating the adjuvant activity of polysaccharides and its mechanisms. These findings expanded current knowledge on the mechanism of action of adjuvant and provide a new target for the design and development of vaccine adjuvants. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Xiong, Beibei AU - Xiong B AD - College of Animal Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, China. FAU - Chen, Xiangfeng AU - Chen X AD - College of Animal Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, China. FAU - Tu, Jue AU - Tu J AD - College of Animal Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, China; Academy of Chinese Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310058, Zhejiang, China. FAU - Han, Ziyi AU - Han Z AD - College of Animal Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, China. FAU - Meng, Xiang AU - Meng X AD - College of Animal Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, China. FAU - Sun, Hongxiang AU - Sun H AD - College of Animal Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, China. Electronic address: sunhx@zju.edu.cn. LA - eng PT - Journal Article DEP - 20230821 PL - Netherlands TA - Int J Biol Macromol JT - International journal of biological macromolecules JID - 7909578 RN - 0 (Adjuvants, Immunologic) RN - 0 (Adjuvants, Pharmaceutic) RN - 0 (Polysaccharides) SB - IM MH - Animals MH - Mice MH - *Actinidia/genetics MH - Mice, Inbred C57BL MH - Adjuvants, Immunologic/pharmacology/metabolism MH - Macrophages MH - Adjuvants, Pharmaceutic MH - Polysaccharides/pharmacology/metabolism OTO - NOTNLM OT - Actinidia eriantha polysaccharide OT - Adjuvant OT - Large intergenic noncoding RNA (lincRNA) 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- 2023/08/24 00:42 MHDA- 2023/11/15 06:43 CRDT- 2023/08/23 19:23 PHST- 2023/04/25 00:00 [received] PHST- 2023/07/17 00:00 [revised] PHST- 2023/08/18 00:00 [accepted] PHST- 2023/11/15 06:43 [medline] PHST- 2023/08/24 00:42 [pubmed] PHST- 2023/08/23 19:23 [entrez] AID - S0141-8130(23)03336-6 [pii] AID - 10.1016/j.ijbiomac.2023.126440 [doi] PST - ppublish SO - Int J Biol Macromol. 2023 Dec 1;252:126440. doi: 10.1016/j.ijbiomac.2023.126440. Epub 2023 Aug 21.