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Single-Cell RNA Sequencing Reveals an Immune Landscape of CD4+ T Cells in Coronary Culprit Plaques With Acute Coronary Syndrome in Humans-Brief Report.
Takeda, Shintaro; Emoto, Takuo; Yamashita, Tomoya; Yamamoto, Hiroyuki; Takaya, Tomofumi; Sawada, Takahiro; Yoshida, Takeshi; Inoue, Masatoshi; Suzuki, Yuya; Hamana, Tomoyo; Inoue, Taishi; Taniguchi, Masayuki; Sasaki, Naoto; Otake, Hiromasa; Ohkawa, Takenao; Furuyashiki, Tomoyuki; Kawai, Hiroya; Hirata, Ken-Ichi.
Afiliación
  • Takeda S; Division of Cardiovascular Medicine, Department of Internal Medicine (S.T., T.E., T. Yamashita, Y.S., T.H., H.O., K.-i.H.), Kobe University Graduate School of Medicine, Japan.
  • Emoto T; Division of Cardiovascular Medicine, Department of Internal Medicine (S.T., T.E., T. Yamashita, Y.S., T.H., H.O., K.-i.H.), Kobe University Graduate School of Medicine, Japan.
  • Yamashita T; Division of Cardiovascular Medicine, Department of Internal Medicine (S.T., T.E., T. Yamashita, Y.S., T.H., H.O., K.-i.H.), Kobe University Graduate School of Medicine, Japan.
  • Yamamoto H; Division of Advanced Medical Science, Kobe University Graduate School of Science, Technology and Innovation, Japan (T. Yamashita).
  • Takaya T; Division of Cardiovascular Medicine, Department of Internal Medicine, Hyogo Prefectural Harima-Himeji General Medical Center, Japan (H.Y., T.T., H.K.).
  • Sawada T; Division of Cardiovascular Medicine, Department of Exploratory and Advanced Search in Cardiology (T.T., H.K.), Kobe University Graduate School of Medicine, Japan.
  • Yoshida T; Division of Cardiovascular Medicine, Department of Internal Medicine, Hyogo Prefectural Harima-Himeji General Medical Center, Japan (H.Y., T.T., H.K.).
  • Inoue M; Division of Cardiovascular Medicine, Kakogawa City Hospital, Japan (T.S.).
  • Suzuki Y; Department of Information and Intelligence Engineering, Kobe University, Japan (T. Yoshida, M.I., T.O.).
  • Hamana T; Department of Information and Intelligence Engineering, Kobe University, Japan (T. Yoshida, M.I., T.O.).
  • Inoue T; Division of Cardiovascular Medicine, Department of Internal Medicine (S.T., T.E., T. Yamashita, Y.S., T.H., H.O., K.-i.H.), Kobe University Graduate School of Medicine, Japan.
  • Taniguchi M; Division of Cardiovascular Medicine, Department of Internal Medicine (S.T., T.E., T. Yamashita, Y.S., T.H., H.O., K.-i.H.), Kobe University Graduate School of Medicine, Japan.
  • Sasaki N; Department of Cardiovascular Surgery (T.I.), Kobe University Graduate School of Medicine, Japan.
  • Otake H; Division of Pharmacology (M.T., T.F.), Kobe University Graduate School of Medicine, Japan.
  • Ohkawa T; Laboratory of Medical Pharmaceutics, Kobe Pharmaceutical University, Japan (N.S.).
  • Furuyashiki T; Division of Cardiovascular Medicine, Department of Internal Medicine (S.T., T.E., T. Yamashita, Y.S., T.H., H.O., K.-i.H.), Kobe University Graduate School of Medicine, Japan.
  • Kawai H; Department of Information and Intelligence Engineering, Kobe University, Japan (T. Yoshida, M.I., T.O.).
  • Hirata KI; Division of Pharmacology (M.T., T.F.), Kobe University Graduate School of Medicine, Japan.
Arterioscler Thromb Vasc Biol ; 44(5): 1135-1143, 2024 05.
Article en En | MEDLINE | ID: mdl-38572648
ABSTRACT

BACKGROUND:

Acute coronary syndrome (ACS) involves plaque-related thrombosis, causing primary ischemic cardiomyopathy or lethal arrhythmia. We previously demonstrated a unique immune landscape of myeloid cells in the culprit plaques causing ACS by using single-cell RNA sequencing. Here, we aimed to characterize T cells in a single-cell level, assess clonal expansion of T cells, and find a therapeutic target to prevent ACS.

METHODS:

We obtained the culprit lesion plaques from 4 patients with chronic coronary syndrome (chronic coronary syndrome plaques) and the culprit lesion plaques from 3 patients with ACS (ACS plaques) who were candidates for percutaneous coronary intervention with directional coronary atherectomy. Live CD45+ immune cells were sorted from each pooled plaque samples and applied to the 10× platform for single-cell RNA sequencing analysis. We also extracted RNA from other 3 ACS plaque samples and conducted unbiased TCR (T-cell receptor) repertoire analysis.

RESULTS:

CD4+ T cells were divided into 5 distinct clusters effector, naive, cytotoxic, CCR7+ (C-C chemokine receptor type 7) central memory, and FOXP3 (forkhead box P3)+ regulatory CD4+ T cells. The proportion of central memory CD4+ T cells was higher in the ACS plaques. Correspondingly, dendritic cells also tended to express more HLAs (human leukocyte antigens) and costimulatory molecules in the ACS plaques. The velocity analysis suggested the differentiation flow from central memory CD4+ T cells into effector CD4+ T cells and that from naive CD4+ T cells into central memory CD4+ T cells in the ACS plaques, which were not observed in the chronic coronary syndrome plaques. The bulk repertoire analysis revealed clonal expansion of TCRs in each patient with ACS and suggested that several peptides in the ACS plaques work as antigens and induced clonal expansion of CD4+ T cells.

CONCLUSIONS:

For the first time, we revealed single cell-level characteristics of CD4+ T cells in patients with ACS. CD4+ T cells could be therapeutic targets of ACS. REGISTRATION URL https//upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000046521; Unique identifier UMIN000040747.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T CD4-Positivos / Síndrome Coronario Agudo / Placa Aterosclerótica / Análisis de la Célula Individual Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Arterioscler Thromb Vasc Biol Asunto de la revista: ANGIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos
Texto completo
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PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T CD4-Positivos / Síndrome Coronario Agudo / Placa Aterosclerótica / Análisis de la Célula Individual Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Arterioscler Thromb Vasc Biol Asunto de la revista: ANGIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos