Transcriptional profiling reveals developmental relationship and distinct biological functions of CD16+ and CD16- monocyte subsets.
Transcriptional profiling reveals developmental relationship and distinct biological functions of CD16+ and CD16- monocyte subsets.
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DOI：
10.1186/1471-2164-10-403
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发表时间：
2009-08-27
期刊：
影响因子：
4.4
通讯作者：
Gabuzda D
中科院分区：
文献类型：
--
作者：
Ancuta P;Liu KY;Misra V;Wacleche VS;Gosselin A;Zhou X;Gabuzda D
人外周血单核细胞(Mo)由CD16(Fc、γ、RIII)和趋化因子受体亚群组成。经典的CD16-Mo表达CCR2并对CCL2作出反应而迁移，而CD16+Mo亚群表达CD16和CX3CR1并迁移到表达CX3CL1的组织中。CD16+Mo产生促炎细胞因子，并在某些炎症条件下扩张，包括脓毒症和艾滋病毒感染。为了深入了解CD16+和CD16-Mo的发育关系和功能，我们检测了健康人外周血中这些Mo亚群的转录谱。在16,328个表达基因中，有2,759个基因在CD16+中差异表达，其中228个和250个基因在CD16+中分别上调和下调2倍。CD16+Mo的区别在于树突状细胞(DC)(SIGLEC10，CD43，RARA)和巨噬细胞(MΦ)(CSF1R/CD115，MafB，CD97，C3aR)的转录上调，以及与DC-T细胞相互作用相关的转录(CXCL16，ICAM-2，LFA-1)，细胞激活(LTB，TNFRSF8，LST1，IFITM1-3，Hmox1，SOD1，WAR，MGL1)，以及对细胞周期的负调控(CDKN1C，MTSS1)，而CD16-Mo的区别在于髓系(CD14，MNDA，TREM1，CD1d，C1qR/CD93)的转录上调GCSFR/CD114、S100A8-9/12)。流式细胞术证实CSF1R、CSF3R、C1QR1、C3AR1、CD1d、CD43、CXCL16和CX3CR1的差异表达。此外，在CD16+Mo中，RARA和KLF2转录本的表达增加与细胞表面皮肤淋巴细胞相关抗原(CLA)的表达缺失相一致，这表明可能存在非皮肤归巢的可能性。这些结果表明，CD16+和CD16-Mo起源于一种常见的髓系前体，CD16+Mo具有更多类似MΦ和DC的转录程序，提示其处于更高级的分化阶段。不同的转录程序，以及它们通过不同的机制重新聚集到组织中，也表明CD16+和CD16-Mo在体内产生了功能不同的DC和MΦ。
Human peripheral blood monocytes (Mo) consist of subsets distinguished by expression of CD16 (FCγRIII) and chemokine receptors. Classical CD16- Mo express CCR2 and migrate in response to CCL2, while a minor CD16+ Mo subset expresses CD16 and CX3CR1 and migrates into tissues expressing CX3CL1. CD16+ Mo produce pro-inflammatory cytokines and are expanded in certain inflammatory conditions including sepsis and HIV infection. To gain insight into the developmental relationship and functions of CD16+ and CD16- Mo, we examined transcriptional profiles of these Mo subsets in peripheral blood from healthy individuals. Of 16,328 expressed genes, 2,759 genes were differentially expressed and 228 and 250 were >2-fold upregulated and downregulated, respectively, in CD16+ compared to CD16- Mo. CD16+ Mo were distinguished by upregulation of transcripts for dendritic cell (DC) (SIGLEC10, CD43, RARA) and macrophage (MΦ) (CSF1R/CD115, MafB, CD97, C3aR) markers together with transcripts relevant for DC-T cell interaction (CXCL16, ICAM-2, LFA-1), cell activation (LTB, TNFRSF8, LST1, IFITM1-3, HMOX1, SOD-1, WARS, MGLL), and negative regulation of the cell cycle (CDKN1C, MTSS1), whereas CD16- Mo were distinguished by upregulation of transcripts for myeloid (CD14, MNDA, TREM1, CD1d, C1qR/CD93) and granulocyte markers (FPR1, GCSFR/CD114, S100A8-9/12). Differential expression of CSF1R, CSF3R, C1QR1, C3AR1, CD1d, CD43, CXCL16, and CX3CR1 was confirmed by flow cytometry. Furthermore, increased expression of RARA and KLF2 transcripts in CD16+ Mo coincided with absence of cell surface cutaneous lymphocyte associated antigen (CLA) expression, indicating potential imprinting for non-skin homing. These results suggest that CD16+ and CD16- Mo originate from a common myeloid precursor, with CD16+ Mo having a more MΦ – and DC-like transcription program suggesting a more advanced stage of differentiation. Distinct transcriptional programs, together with their recruitment into tissues via different mechanisms, also suggest that CD16+ and CD16- Mo give rise to functionally distinct DC and MΦ in vivo.
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