PMID- 35222381 OWN - NLM STAT- MEDLINE DCOM- 20220408 LR - 20220408 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 13 DP - 2022 TI - Intravenous Immunoglobulin Therapy Restores the Quantity and Phenotype of Circulating Dendritic Cells and CD4(+) T Cells in Children With Acute Kawasaki Disease. PG - 802690 LID - 10.3389/fimmu.2022.802690 [doi] LID - 802690 AB - BACKGROUND: Intravenous immunoglobulin (IVIG) showed its therapeutic efficacy on Kawasaki disease (KD). However, the mechanisms by which it reduces systemic inflammation are not completely understood. Dendritic cells (DCs) and T cells play critical roles in the pathogenic processes of immune disorders. Assessing the quantity of DC subsets and T cells and identifying functional molecules present on these cells, which provide information about KD, in the peripheral blood may provide new insights into the mechanisms of immunoglobulin therapy. METHODS: In total, 54 patients with KD and 27 age-matched healthy controls (HCs) were included in this study. The number, percentage, and phenotype of DC subsets and CD4(+) T cells in peripheral blood were analyzed through flow cytometry. RESULTS: Patients with KD exhibited fewer peripheral DC subsets and CD4(+) T cells than HCs. Human leucocyte antigen-DR (HLA-DR) expression was reduced on CD1c(+) myeloid DCs (CD1c(+) mDCs), whereas that on plasmacytoid DCs (pDCs) did not change significantly. Both pDCs and CD1c(+) mDCs displayed significantly reduced expression of co-stimulatory molecules, including CD40, CD86. pDCs and CD1c(+) mDCs presented an immature or tolerant phenotype in acute stages of KD. Number of circulating pDC and CD1c(+) mDC significantly inversely correlated with plasma interleukin-6 (IL-6) levels in KD patients pre-IVIG treatment. No significant differences were found concerning the DC subsets and CD4(+) T cells in patients with KD with and without coronary artery lesions. Importantly, these altered quantity and phenotypes on DC subsets and CD4(+) T cells were restored to a great extent post-IVIG treatment. T helper (Th) subsets including Th1 and Th2 among CD4(+) T cells did not show alteration pre- and post-IVIG treatment, although the Th1-related cytokine IFN-gamma level in plasma increased dramatically in patients with KD pre-IVIG treatment. CONCLUSIONS: pDCs and CD1c(+) mDCs presented an immature or tolerant phenotype in acute stages of KD, IVIG treatment restored the quantity and functional molecules of DCs and CD4(+) T cells to distinct levels in vivo, indicating the involvement of DCs and CD4(+) T cells in the inflammation in KD. The findings provide insights into the immunomodulatory actions of IVIG in KD. CI - Copyright (c) 2022 Wang, Chen, Zhang, Zhang, Sun, Lv, Wang, Shen, Zhou, Chen, Zhang, Meng, Zhou, Bai and Huang. FAU - Wang, Nana AU - Wang N AD - Department of Cardiology, Children's Hospital of Soochow University, Suzhou, China. FAU - Chen, Zhongyue AU - Chen Z AD - Department of Cardiology, Children's Hospital of Soochow University, Suzhou, China. FAU - Zhang, Fan AU - Zhang F AD - Department of Cardiology, Children's Hospital of Soochow University, Suzhou, China. FAU - Zhang, Qianwen AU - Zhang Q AD - Department of Cardiology, Children's Hospital of Soochow University, Suzhou, China. FAU - Sun, Ling AU - Sun L AD - Department of Cardiology, Children's Hospital of Soochow University, Suzhou, China. FAU - Lv, Haitao AU - Lv H AD - Department of Cardiology, Children's Hospital of Soochow University, Suzhou, China. FAU - Wang, Bo AU - Wang B AD - Department of Cardiology, Children's Hospital of Soochow University, Suzhou, China. FAU - Shen, Jie AU - Shen J AD - Department of Cardiology, Children's Hospital of Soochow University, Suzhou, China. FAU - Zhou, Xufang AU - Zhou X AD - Department of Cardiology, Children's Hospital of Soochow University, Suzhou, China. FAU - Chen, Feiyan AU - Chen F AD - Department of Cardiology, Children's Hospital of Soochow University, Suzhou, China. FAU - Zhang, Binwei AU - Zhang B AD - Department of Cardiology, Children's Hospital of Soochow University, Suzhou, China. FAU - Meng, Lijun AU - Meng L AD - Department of Hematology, Children's Hospital of Soochow University, Suzhou, China. FAU - Zhou, Huiting AU - Zhou H AD - Pediatric Research Institute of Soochow University, Suzhou, China. FAU - Bai, ZhenJiang AU - Bai Z AD - Department of Pediatric Intensive Care Unit, Children Hospital of Soochow University, Suzhou, China. FAU - Huang, Jie AU - Huang J AD - Department of Cardiology, Children's Hospital of Soochow University, Suzhou, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220210 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Immunoglobulins, Intravenous) SB - IM MH - CD4-Positive T-Lymphocytes MH - Dendritic Cells MH - Humans MH - *Immunoglobulins, Intravenous/therapeutic use MH - Inflammation/metabolism MH - *Mucocutaneous Lymph Node Syndrome/drug therapy/metabolism MH - Phenotype MH - T-Lymphocytes/metabolism PMC - PMC8866170 OTO - NOTNLM OT - CD4+ T cells OT - Kawasaki disease OT - dendritic cells OT - immune disorders OT - intravenous immunoglobulin COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/03/01 06:00 MHDA- 2022/04/09 06:00 PMCR- 2022/01/01 CRDT- 2022/02/28 05:34 PHST- 2021/10/27 00:00 [received] PHST- 2022/01/13 00:00 [accepted] PHST- 2022/02/28 05:34 [entrez] PHST- 2022/03/01 06:00 [pubmed] PHST- 2022/04/09 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2022.802690 [doi] PST - epublish SO - Front Immunol. 2022 Feb 10;13:802690. doi: 10.3389/fimmu.2022.802690. eCollection 2022.