Myeloid-derived suppressor cells exacerbate poly(I:C)-induced lung inflammation in mice with renal injury and older mice

Zhiqi Xie; Haoyang Zhou; Masanori Obana; Yasushi Fujio; Naoki Okada; Masashi Tachibana

doi:10.3389/fimmu.2023.1243851

Myeloid-derived suppressor cells exacerbate poly(I:C)-induced lung inflammation in mice with renal injury and older mice

Front Immunol. 2023 Sep 25:14:1243851. doi: 10.3389/fimmu.2023.1243851. eCollection 2023.

Authors

Zhiqi Xie^{1

2}, Haoyang Zhou², Masanori Obana^{3

4

5

6}, Yasushi Fujio^{3

4

5}, Naoki Okada², Masashi Tachibana^{2

6

7}

Affiliations

¹ Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang, School of Medicine, Hangzhou City University, Hangzhou, Zhejiang, China.
² Project for Vaccine and Immune Regulation, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
³ Laboratory of Clinical Science and Biomedicine, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
⁴ Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Osaka, Japan.
⁵ Center for Infectious Disease Education and Research (CiDER), Osaka University, Osaka, Japan.
⁶ Global Center for Medical Engineering and Informatics, Osaka University, Osaka, Japan.
⁷ Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.

Abstract

Viral pneumonia is a global health burden with a high mortality rate, especially in the elderly and in patients with underlying diseases. Recent studies have found that myeloid-derived suppressor cells (MDSCs) are abundant in these patient groups; however, their roles in the progression of viral pneumonia remain unclear. In this study, we observed a substantial increase in MDSCs in a mouse model of renal ischemia/reperfusion (I/R) injury and in older mice. When intranasal polyinosinic-polycytidylic acid (poly(I:C)) administration was used to mimic viral pneumonia, mice with renal I/R injury exhibited more severe lung inflammation than sham mice challenged with poly(I:C). In addition, MDSC depletion attenuated lung inflammation in mice with I/R injury. Similar results were obtained in older mice compared with those in young mice. Furthermore, adoptive transfer of in vitro-differentiated MDSCs exacerbated poly(I:C)-induced lung inflammation. Taken together, these experimental results suggest that the increased proportion of MDSCs in mice with renal I/R injury and in older mice exacerbates poly(I:C)-induced lung inflammation. These findings have important implications for the treatment and prevention of severe lung inflammation caused by viral pneumonia.

Keywords: MDSC; aging; lung inflammation; poly(I:C); renal ischemia/reperfusion injury.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Animals
Disease Models, Animal
Humans
Kidney
Mice
Myeloid-Derived Suppressor Cells*
Pneumonia, Viral*
Poly I-C

Substances

Poly I-C

Grants and funding

This work was supported in part by JSPS KAKENHI (Grant No. JP22H03533, Grants-in-aid for Scientific Research (B)) and a grant from The Drug Discovery Science Division, Open and Transdisciplinary Research Initiatives, Osaka University (M.T.). This research was partially supported by the Zhejiang Provincial Natural Science Foundation of China (Grant No. LQ23H160001) (Z.X.). This research was also partially supported by the Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) from AMED (Grant Nos. JP22ama121052 and JP22ama121054).