The final, formatted version of the article will be published soon.
ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1455925
Single-cell RNA Sequencing Uncovers Molecular Mechanisms of Intravenous Immunoglobulin Plus Methylprednisolone in Kawasaki Disease: Attenuated Monocyte-Driven Inflammation and Improved NK Cell Cytotoxicity
Provisionally accepted
Minna Yang
1
Yeshi Chen
1
Chenhui Feng
1*
Mingming Zhang
2
Hongmao Wang
2*
Yang Zheng
3*
Xiaohui Li
1,2,3*- 1 Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, China
- 2 Department of Cardiovascular Medicine, Children's Hospital of Capital Institute of Pediatrics, Beijing, Beijing Municipality, China
- 3 Peking Union Medical College Graduate School, Beijing, China
Intravenous immunoglobulin (IVIG) plus methylprednisolone as initial intensive therapy or additional therapy in Kawasaki disease (KD) has been used in clinical practice. However, its molecular and cellular mechanism is unclear. We performed single-cell analysis on 14 peripheral blood mononuclear cell (PBMC) samples obtained from 7 KD patients who received either IVIG monotherapy or IVIG plus methylprednisolone therapy. This encompassed 4 samples from KD patients collected before and after IVIG treatment, as well as 3 samples from KD patients before and after IVIG plus methylprednisolone therapy. Both IVIG monotherapy and IVIG plus methylprednisolone therapy can increase lymphocyte counts (e.g. CD4+T, CD8+T, and γδT cells) to address lymphopenia. They can also decrease monocyte counts and repress the expression of S100A12, NLRP3, and genes associated with immune-cell migration in monocytes. IVIG combined with methylprednisolone downregulates more monocyte-driven inflammatory pathways than IVIG alone. Additionally, this combination uniquely enhances NK cell cytotoxicity by modulating receptor homeostasis, while significantly upregulating interferon-related genes in CD4+ T cells, CD8+ T cells, and B cells, particularly type I interferons. In conclusion, the combination of IVIG with methylprednisolone attenuated monocyte-driven inflammation and improved NK cell cytotoxicity which might provide clues for pediatricians to consider treatment options for children with KD. Whether the monocytedriven hyperinflammatory state and NK cell function can be indicators for the clinical choice of IVIG with methylprednisolone therapy in KD needs further investigation.
Keywords: kawasaki disease, Methylprednisolone, single-cell RNA transcriptome sequencing, Inflammatory Response, NK cell cytotoxicity
Received: 27 Jun 2024; Accepted: 04 Oct 2024.
Copyright: © 2024 Yang, Chen, Feng, Zhang, Wang, Zheng and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Chenhui Feng, Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, China
Hongmao Wang, Department of Cardiovascular Medicine, Children's Hospital of Capital Institute of Pediatrics, Beijing, 100005, Beijing Municipality, China
Yang Zheng, Peking Union Medical College Graduate School, Beijing, 100730, China
Xiaohui Li, Capital Institute of Pediatrics-Peking University Teaching Hospital, Beijing, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.