mRNA–miRNA integration analysis of T-cell exhaustion in sepsis from community-acquired pneumonia

Oda, Sayaka; Matsumoto, Hisatake; Togami, Yuki; Yoshimura, Jumpei; Ito, Hiroshi; Onishi, Shinya; Muratsu, Arisa; Mitsuyama, Yumi; Okuzaki, Daisuke; Ogura, Hiroshi; Tanaka, Susumu; Oda, Jun

doi:https://doi.org/10.1002/ams2.70054

mRNA–miRNA integration analysis of T-cell exhaustion in sepsis from community-acquired pneumonia

Oda, Sayaka; Matsumoto, Hisatake; Togami, Yuki et al.

Acute Medicine & Surgery, 2025, 12(1), e70054

Number of Access:1,768（2025-08-16 03:18 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/101082

Link to primary information

File	Format	Terms of use	Size	Views	Date.Available	Description	information
AcuteMedicine&Surgery_12_1_e70054	pdf	None	2.16 MB	30	2025.04.25

Creative Commons : Attribution - NonCommercial

Item Information

Output File Export EndNote Basic Export Mendeley

Title	mRNA–miRNA integration analysis of T-cell exhaustion in sepsis from community-acquired pneumonia
Creator	CreatorName Oda, Sayaka
	NRID 1000070644003 1000070644003 researchmap permalink 38283828 38283828 Scopus Author ID 36632584800 36632584800 CreatorName Matsumoto, Hisatake
	NRID 1000050866936 1000050866936 researchmap permalink togyuki togyuki CreatorName Togami, Yuki
	NRID 1000030835202 1000030835202 CreatorName Yoshimura, Jumpei
	NRID 1000080836594 1000080836594 researchmap permalink 1009hiroshi.ito 1009hiroshi.ito CreatorName Ito, Hiroshi
	CreatorName Onishi, Shinya
	NRID 1000090737199 1000090737199 ORCID 0000-0002-7035-7684 0000-0002-7035-7684 researchmap permalink cocoa cocoa CreatorName Muratsu, Arisa
	CreatorName Mitsuyama, Yumi
	NRID 1000000346131 1000000346131 ORCID 0000-0002-4552-783X 0000-0002-4552-783X researchmap permalink read0092307 read0092307 Scopus Author ID 6506703054 6506703054 CreatorName Okuzaki, Daisuke
	NRID 1000070301265 1000070301265 researchmap permalink read0054647 read0054647 Scopus Author ID 7202495132 7202495132 CreatorName Ogura, Hiroshi
	NRID 1000000367541 1000000367541 ORCID 0000-0002-0306-3627 0000-0002-0306-3627 researchmap permalink mes5 mes5 Scopus Author ID 56395750500 56395750500 CreatorName Tanaka, Susumu
	NRID 1000060459500 1000060459500 ORCID 0000-0002-8254-3716 0000-0002-8254-3716 researchmap permalink read0068529 read0068529 Scopus Author ID 56210537000 56210537000 CreatorName Oda, Jun
Subject	community-acquired pneumonia
	microRNAs
	mRNAs
	PD-1/PDL1
	T-cell exhaustion
Description	mRNA–miRNA integration analysis of T-cell exhaustion in sepsis from community-acquired pneumonia. Acute Medicine & Surgery 12(1), e70054 (2025); https://doi.org/10.1002/ams2.70054.
Abstract	Aim: Community-acquired pneumonia is an acute lung infection in patients without recent healthcare exposure that can progress to severe sepsis. Despite the well-established influence of miRNAs on inflammation, their specific roles in pneumonia-associated sepsis remain underexplored. In this pilot study, we aimed to provide insights into the pathogenesis of community-acquired pneumonia-associated sepsis by performing an integrative mRNA–miRNA analysis to identify key cellular signaling pathways and potential molecular targets for future research and treatment development. Methods: We conducted a prospective, observational, single-center study including 14 critically ill patients with community-acquired pneumonia-associated sepsis and 15 healthy controls (median age: 78 [interquartile range 67.3–83.5] and 55 [interquartile range 40.5–59.0] years, respectively). Results: Eleven patients required ventilatory support, and six met the diagnostic criteria for septic shock. All patients survived. RNA sequencing revealed 1209 upregulated and 1461 downregulated differentially expressed genes for mRNAs (false discovery rate < 0.05, \|log2 fold change\| >1.2), 51 upregulated and 21 downregulated genes for miRNAs, and 646 upregulated and 1274 downregulated for mRNA related to miRNAs. Canonical pathway analysis revealed activation of the programmed death-1/programmed death-ligand-1 cancer immunotherapy pathway and suppression of the Th1 pathway, indicating T-cell exhaustion in the acute phase of community-acquired pneumonia-associated sepsis. Conclusion: This study provides valuable insights into the molecular mechanisms underlying CAP-associated sepsis, confirming the occurrence of immune dysregulation, particularly T-cell exhaustion. Our findings suggest that specific miRNAs and signaling pathways identified here may serve as potential therapeutic targets or biomarkers.
Publisher	Wiley
Source Title	Acute Medicine & Surgery
Volume (Issue)	12(1)
Page	e70054
Date of Issued	2025-04-02
Language	English
Handle URL	https://hdl.handle.net/11094/101082
PISSN	20528817
eISSN	20528817
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1002/ams2.70054
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Acute Medicine & Surgery. 2025, 12(1), p. e70054
DC.title	mRNA–miRNA integration analysis of T-cell exhaustion in sepsis from community-acquired pneumonia
DC.creator	Oda, Sayaka
	Matsumoto, Hisatake
	Togami, Yuki
	Yoshimura, Jumpei
	Ito, Hiroshi
	Onishi, Shinya
	Muratsu, Arisa
	Mitsuyama, Yumi
	Okuzaki, Daisuke
	Ogura, Hiroshi
	Tanaka, Susumu
	Oda, Jun
DC.publisher	Wiley
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-04-02
DC.identifier	https://doi.org/10.1002/ams2.70054
DC.subject	community-acquired pneumonia
	microRNAs
	mRNAs
	PD-1/PDL1
	T-cell exhaustion
DC.description	mRNA–miRNA integration analysis of T-cell exhaustion in sepsis from community-acquired pneumonia. Acute Medicine & Surgery 12(1), e70054 (2025); https://doi.org/10.1002/ams2.70054.
DCTERMS.abstract	Aim: Community-acquired pneumonia is an acute lung infection in patients without recent healthcare exposure that can progress to severe sepsis. Despite the well-established influence of miRNAs on inflammation, their specific roles in pneumonia-associated sepsis remain underexplored. In this pilot study, we aimed to provide insights into the pathogenesis of community-acquired pneumonia-associated sepsis by performing an integrative mRNA–miRNA analysis to identify key cellular signaling pathways and potential molecular targets for future research and treatment development. Methods: We conducted a prospective, observational, single-center study including 14 critically ill patients with community-acquired pneumonia-associated sepsis and 15 healthy controls (median age: 78 [interquartile range 67.3–83.5] and 55 [interquartile range 40.5–59.0] years, respectively). Results: Eleven patients required ventilatory support, and six met the diagnostic criteria for septic shock. All patients survived. RNA sequencing revealed 1209 upregulated and 1461 downregulated differentially expressed genes for mRNAs (false discovery rate < 0.05, \|log2 fold change\| >1.2), 51 upregulated and 21 downregulated genes for miRNAs, and 646 upregulated and 1274 downregulated for mRNA related to miRNAs. Canonical pathway analysis revealed activation of the programmed death-1/programmed death-ligand-1 cancer immunotherapy pathway and suppression of the Th1 pathway, indicating T-cell exhaustion in the acute phase of community-acquired pneumonia-associated sepsis. Conclusion: This study provides valuable insights into the molecular mechanisms underlying CAP-associated sepsis, confirming the occurrence of immune dysregulation, particularly T-cell exhaustion. Our findings suggest that specific miRNAs and signaling pathways identified here may serve as potential therapeutic targets or biomarkers.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
DC.format	101082
citation_title	mRNA–miRNA integration analysis of T-cell exhaustion in sepsis from community-acquired pneumonia
citation_author	Oda, Sayaka
	Matsumoto, Hisatake
	Togami, Yuki
	Yoshimura, Jumpei
	Ito, Hiroshi
	Onishi, Shinya
	Muratsu, Arisa
	Mitsuyama, Yumi
	Okuzaki, Daisuke
	Ogura, Hiroshi
	Tanaka, Susumu
	Oda, Jun
citation_publisher	Wiley
citation_language	English
citation_date	2025-04-02
citation_journal_title	Acute Medicine & Surgery
citation_volume	12
citation_issue	1
citation_firstpage	e70054
citation_doi	https://doi.org/10.1002/ams2.70054
citation_public_url	https://hdl.handle.net/11094/101082

mRNA–miRNA integration analysis of T-cell exhaustion in sepsis from community-acquired pneumonia

Link to primary information

Item Information

Show details