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

アクセス数:15件（2025-04-28 14:12 集計）

固定URL: https://hdl.handle.net/11094/101082

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タイトル	mRNA–miRNA integration analysis of T-cell exhaustion in sepsis from community-acquired pneumonia
著者	著者名 Oda, Sayaka
	NRID 1000070644003 1000070644003 researchmap permalink 38283828 38283828 Scopus Author ID 36632584800 36632584800 著者名 Matsumoto, Hisatake
	NRID 1000050866936 1000050866936 researchmap permalink togyuki togyuki 著者名 Togami, Yuki
	NRID 1000030835202 1000030835202 著者名 Yoshimura, Jumpei
	NRID 1000080836594 1000080836594 researchmap permalink 1009hiroshi.ito 1009hiroshi.ito 著者名 Ito, Hiroshi
	著者名 Onishi, Shinya
	NRID 1000090737199 1000090737199 ORCID 0000-0002-7035-7684 0000-0002-7035-7684 researchmap permalink cocoa cocoa 著者名 Muratsu, Arisa
	著者名 Mitsuyama, Yumi
	NRID 1000000346131 1000000346131 ORCID 0000-0002-4552-783X 0000-0002-4552-783X researchmap permalink read0092307 read0092307 Scopus Author ID 6506703054 6506703054 著者名 Okuzaki, Daisuke
	NRID 1000070301265 1000070301265 researchmap permalink read0054647 read0054647 Scopus Author ID 7202495132 7202495132 著者名 Ogura, Hiroshi
	NRID 1000000367541 1000000367541 ORCID 0000-0002-0306-3627 0000-0002-0306-3627 researchmap permalink mes5 mes5 Scopus Author ID 56395750500 56395750500 著者名 Tanaka, Susumu
	NRID 1000060459500 1000060459500 ORCID 0000-0002-8254-3716 0000-0002-8254-3716 researchmap permalink read0068529 read0068529 Scopus Author ID 56210537000 56210537000 著者名 Oda, Jun
キーワード等	community-acquired pneumonia
	microRNAs
	mRNAs
	PD-1/PDL1
	T-cell exhaustion
内容	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.
抄録	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.
出版者	Wiley
収録物名	Acute Medicine & Surgery
巻(号)	12(1)
ページ	e70054
刊行年月	2025-04-02
言語	英語
ハンドルURL	https://hdl.handle.net/11094/101082
PISSN	20528817
eISSN	20528817
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1002/ams2.70054
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	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	英語
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	英語
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

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