Single-Cell Profiling Reveals Divergent, Globally Patterned Immune Responses in Murine Skin Inflammation.
Single-Cell Profiling Reveals Divergent, Globally Patterned Immune Responses in Murine Skin Inflammation.
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单细胞分析揭示了小鼠皮肤炎症中不同的、全局模式的免疫反应。
DOI：
10.1016/j.isci.2020.101582
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发表时间：
2020-10-23
期刊：
影响因子：
5.8
通讯作者：
Cheng JB
中科院分区：
文献类型：
--
作者：
Liu Y;Cook C;Sedgewick AJ;Zhang S;Fassett MS;Ricardo-Gonzalez RR;Harirchian P;Kashem SW;Hanakawa S;Leistico JR;North JP;Taylor MA;Zhang W;Man MQ;Charruyer A;Beliakova-Bethell N;Benz SC;Ghadially R;Mauro TM;Kaplan DH;Kabashima K;Choi J;Song JS;Cho RJ;Cheng JB
炎症反应的异质性阻碍了在激活过程中对不同免疫细胞群的高分辨率解剖。在使用咪喹莫特和恶唑酮皮炎模型诱导炎症后，我们通过单细胞RNA测序来表征小鼠皮肤免疫细胞。我们确定了13个CD45+亚群，它们广泛地代表了最具功能特征的免疫细胞类型。恶唑酮可在T细胞和抗原提呈细胞(APC)中普遍上调JAK2/STAT3的表达。恶唑酮还可诱导新渗入的嗜碱性粒细胞表达IL4/IL13，尤其是在APC中诱导IL4ra和Ccl24的表达。相比之下，咪喹莫特广泛上调IL17/IL22和CCl4/CCL5。对单细胞炎症转录反应的比较分析表明，APC对恶唑酮的反应受到细胞特性的严格限制，而咪喹莫特并行地在多个APC群体上实施共享程序。这些全球分子模式不仅在系统水平上对比免疫反应，而且还表明，通过与已知特征的比较，最终可以推断出新的炎症来源的机制。恶唑酮可跨T细胞普遍上调JAK2/STAT3的表达，APC IL4/IL13在皮肤中的诱导以嗜碱性粒细胞为主，咪喹莫特广泛增加IL17/IL22和CCL4/CCL5，延伸至非T细胞，与咪喹莫特免疫学相比，恶唑酮可诱导更多高度区域化的免疫细胞反应
Inflammatory response heterogeneity has impeded high-resolution dissection of diverse immune cell populations during activation. We characterize mouse cutaneous immune cells by single-cell RNA sequencing, after inducing inflammation using imiquimod and oxazolone dermatitis models. We identify 13 CD45+ subpopulations, which broadly represent most functionally characterized immune cell types. Oxazolone pervasively upregulates Jak2/Stat3 expression across T cells and antigen-presenting cells (APCs). Oxazolone also induces Il4/Il13 expression in newly infiltrating basophils, and Il4ra and Ccl24, most prominently in APCs. In contrast, imiquimod broadly upregulates Il17/Il22 and Ccl4/Ccl5. A comparative analysis of single-cell inflammatory transcriptional responses reveals that APC response to oxazolone is tightly restricted by cell identity, whereas imiquimod enforces shared programs on multiple APC populations in parallel. These global molecular patterns not only contrast immune responses on a systems level but also suggest that the mechanisms of new sources of inflammation can eventually be deduced by comparison to known signatures. Oxazolone pervasively upregulates Jak2/Stat3 expression across T cells and APCs Il4/Il13 induction in skin by oxazolone is dominated by infiltrating basophils Imiquimod broadly increases Il17/Il22 and Ccl4/Ccl5, extending to non-T cells Oxazolone induces more highly compartmentalized immune cell responses than imiquimod Immunology; Systems Biology
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DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
3.1
作者：
Fujii, Yasutomo;Sengoku, Takanori
通讯作者：
Sengoku, Takanori
DOI：
10.1126/science.aad0616
发表时间：
2015-10-16
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kim HJ;Barnitz RA;Kreslavsky T;Brown FD;Moffett H;Lemieux ME;Kaygusuz Y;Meissner T;Holderried TA;Chan S;Kastner P;Haining WN;Cantor H
通讯作者：
Cantor H
影响因子：
15.9
作者：
Akahoshi, Mitsuteru;Song, Chang Ho;Galli, Stephen J.
通讯作者：
Galli, Stephen J.
影响因子：
6.5
作者：
Kim, Nari;Bae, Ki Beom;Ryoo, Zae Young
通讯作者：
Ryoo, Zae Young