Single-cell profiling reveals inflammatory polarization of human carotid versus femoral plaque leukocytes.
Single-cell profiling reveals inflammatory polarization of human carotid versus femoral plaque leukocytes.
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DOI：
10.1172/jci.insight.171359
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发表时间：
2023-09-08
期刊：
影响因子：
8
通讯作者：
Feinstein, Matthew J.
中科院分区：
文献类型：
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作者：
Slysz, Joshua;Sinha, Arjun;Deberge, Matthew;Singh, Shalini;Avgousti, Harris;Lee, Inhyeok;Glinton, Kristofor;Nagasaka, Reina;Dalal, Prarthana;Alexandria, Shaina;Wai, Ching Man;Tellez, Ricardo;Vescovo, Mariavittoria;Sunderraj, Ashwin;Wang, Xinkun;Schipma, Matthew;Sisk, Ryan;Gulati, Rishab;Vallejo, Jenifer;Saigusa, Ryosuke;Lloyd-Jones, Donald M.;Lomasney, Jon;Weinberg, Samuel;Ho, Karen;Ley, Klaus;Giannarelli, Chiara;Thorp, Edward B.;Feinstein, Matthew J.
在组织学上，股骨动脉粥样硬化斑块的炎症性比颈动脉斑块小，但关于这些部位的比较免疫景观和极化的细胞水平数据有限。我们使用单细胞RNA-Seq （scRNA-Seq; n = 13）、流式细胞术（n = 24）和免疫组化（n = 12）研究了49例接受股骨（n = 23）或颈动脉（n = 26）内膜切除术的患者斑块内白细胞表型和转录极化。从股骨斑块（n = 9, 35,265个细胞）和颈动脉斑块（n = 4, 30,655个细胞）中CD45+选择的白细胞的比较scRNA-Seq显示出不同的转录谱。颈动脉斑块中炎性泡沫细胞样巨噬细胞和单核细胞组成的髓样细胞比例较高，而非炎性泡沫细胞样巨噬细胞和过表达lyve1的巨噬细胞组成的髓样细胞比例较高（均P < 0.001）。在一个单独的验证队列中，流式细胞术观察到颈动脉与斑块中CCR2+巨噬细胞的显著比较过剩。B细胞在股骨斑块中更为普遍，表现出相对抗炎的特征，而细胞毒性CD8+ T细胞在颈动脉斑块中更为普遍。总之，与人颈动脉斑块相比，人股骨斑块表现出不同的巨噬细胞表型和转录谱，以及CD8+ T细胞群的减少
Femoral atherosclerotic plaques are less inflammatory than carotid plaques histologically, but limited cell-level data exist regarding comparative immune landscapes and polarization at these sites. We investigated intraplaque leukocyte phenotypes and transcriptional polarization in 49 patients undergoing femoral (n = 23) or carotid (n = 26) endarterectomy using single-cell RNA-Seq (scRNA-Seq; n = 13), flow cytometry (n = 24), and IHC (n = 12). Comparative scRNA-Seq of CD45+-selected leukocytes from femoral (n = 9; 35,265 cells) and carotid (n = 4; 30,655 cells) plaque revealed distinct transcriptional profiles. Inflammatory foam cell–like macrophages and monocytes comprised higher proportions of myeloid cells in carotid plaques, whereas noninflammatory foam cell–like macrophages and LYVE1-overexpressing macrophages comprised higher proportions of myeloid cells in femoral plaque (P < 0.001 for all). A significant comparative excess of CCR2+ macrophages in carotid versus plaque was observed by flow cytometry in a separate validation cohort. B cells were more prevalent and exhibited a comparatively antiinflammatory profile in femoral plaque, whereas cytotoxic CD8+ T cells were more prevalent in carotid plaque. In conclusion, human femoral plaques exhibit distinct macrophage phenotypic and transcriptional profiles as well as diminished CD8+ T cell populations compared with human carotid plaques
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DOI：
10.1126/science.abl5197
发表时间：
2022-05-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Domínguez Conde C;Xu C;Jarvis LB;Rainbow DB;Wells SB;Gomes T;Howlett SK;Suchanek O;Polanski K;King HW;Mamanova L;Huang N;Szabo PA;Richardson L;Bolt L;Fasouli ES;Mahbubani KT;Prete M;Tuck L;Richoz N;Tuong ZK;Campos L;Mousa HS;Needham EJ;Pritchard S;Li T;Elmentaite R;Park J;Rahmani E;Chen D;Menon DK;Bayraktar OA;James LK;Meyer KB;Yosef N;Clatworthy MR;Sims PA;Farber DL;Saeb-Parsy K;Jones JL;Teichmann SA
通讯作者：
Teichmann SA
影响因子：
82.9
作者：
Fernandez, Dawn M.;Rahman, Adeeb H.;Giannarelli, Chiara
通讯作者：
Giannarelli, Chiara
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
5.4
作者：
Boniakowski AE;Kimball AS;Joshi A;Schaller M;Davis FM;denDekker A;Obi AT;Moore BB;Kunkel SL;Gallagher KA
通讯作者：
Gallagher KA
DOI：
10.4049/jimmunol.1700551
发表时间：
2017-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Das A;Rouault-Pierre K;Kamdar S;Gomez-Tourino I;Wood K;Donaldson I;Mein CA;Bonnet D;Hayday AC;Gibbons DL
通讯作者：
Gibbons DL