Immune cell subset differentiation and tissue inflammation

Fang, Pu; Li, Xinyuan; Dai, Jin; Cole, Lauren; Camacho, Javier Andres; Zhang, Yuling; Ji, Yong; Wang, Jingfeng; Yang, Xiao-Feng; Wang, Hong

doi:10.1186/s13045-018-0637-x

Journal of Hematology & Oncology

Table 2 Characterization of myeloid cell subsets

From: Immune cell subset differentiation and tissue inflammation

Subsets		Markers	Frequency	Cytokines	Functions
DC	cDC	CD11c⁺MHCII⁺CD141⁺(BDCA3⁺)XCR1⁺CLEC9A⁺FLT3⁺CD103⁺	5~10% in blood	IL-12, IFN-III	↑IFN-IIICross-present Ag
	cDC	CD11c⁺MHCII⁺(BDCA1⁺)CD172a⁺CD11b⁺FLT3⁺	45–50% in blood	IL-23?	Present Ag
	pDC	BDCA2⁺LILRA4⁺CD45RA⁺	45–50% in blood	IFNα	Sense pathogenActivate IC
	mDC	MHCII⁺CD11c⁺CD86⁺CD40⁺CD80⁺CD83⁺CCR7⁺CD14⁻	Induced by inflammation	TNFα, iNOSIL-12, IL-23	Cross-present Ag
MC	Classical	CD14⁺CD16⁻CXCR1⁺ CXCR2⁺CD62L⁺	80–95% in MNC	ROS, NO, MPOIFN-I, IL-1α, TNFIL-6, IL-8, CCL2	Phagocytosis↑Inflammation
	Intermediate	CD14⁺CD16^+CD64^intCCR1^intCCR2^int CX3CR1^int CD11b^int CD33^int CD115^int CD40⁺ CD54⁺ HLA-DR⁺	2–11% in MNC	ROS, NO, MPOIFN-I, IL-1α, TNFIL-6, IL-8 CCL2	↑Inflammation
	Non-classical	CD14⁻CD16⁺	2–8% in MNC	TNF, IL-1β, CCL3	Patrol, repair tissue
	CD40	CD14⁺CD40⁺	64% in PBMC	TNFα, IL-6	↑Inflammation
MØ	M1	iNOS⁺CXCL11⁺IL-12high IL-23^highIL-10^low	1% in gastric tissue	IL-6, TNFαiNOS, IL-12	Microbicidal↑Inflammation
	M2a	FIZZ1⁺Arg1⁺IL-12^lowIL-23^low	1% in gastric tissue	IL-10	↓InflammationHeal woundRepair tissue
	M2b	CD80^highCD14^highHLA-DR^lowIL-12^lowIL-23^low	0 in PBMC	IL-10	Activate Th2↓Inflammation
	M2c	CD86^lowHLA-DR^lowCD163⁺TLR4^highIL-12^lowIL-23^low	2.4% in CD68⁺ MØ	CCL18	↓InflammationDeposit matrixRemodel tissue
	M4	MMP7⁺MR⁺S100A8⁺CD68⁺	31.7% in CD68⁺ MØ from coronary artery	CD86, IL-6, TNFα	↑Inflammation
	Mhem	HOMX1⁺CD163⁺	25% in thrombosis	IL-10	↓Lipid accumulationRetain iron, ↓Inflammation

Four kinds of dendritic cells (DC) can be defined in human based in part on their functional specialization: monocyte-derived DC (mDC), CD103+ classical/conventional dendritic cell (cDC), CD11b + cDC, and plasmocytoid dendritic cell (pDC). mDC exhibit a strong costimulatory capacity for TC activation. cDC are the most efficient cell type for priming and functional polarization of TC. pDCs can secrete high concentrations of interferon (IFN)-I (mainly IFN-α). In humans, there are three populations of monocytes (MC), as defined by the expression of CD14 and CD16 (CD14++CD16−, CD14+CD16+, and CD14+CD16++). The CD14++CD16− MC represent 80% to 90% of blood MC, express high levels of the chemokine receptor C-C chemokine receptor type 2 (CCR2) and low levels of CX3C chemokine receptor 1 (CX3CR1), and produce IL-10 rather than TNF and IL-1 in response to lipopolysaccharide (LPS) in vitro. CD14+CD16+ MC express the Fc receptors CD64 and CD32, have phagocytic activity, and are entirely responsible for the production of tumor necrosis factor-α (TNF-α) and IL-1 in response to LPS. In contrast, CD14+CD16++ MC lack the expression of other Fc receptors, are poorly phagocytic, and do not produce TNF-α or IL-1 in response to LPS. Our lab recently identified CD40+ MC as a stronger inflammatory subset related to chronic kidney disease (CKD). Macrophages (MØ) also display phenotypic heterogeneity. Depending on the stimuli, M0 MØ could polarize towards the pro-inflammatory M1 subset by lipopolysaccharide or IFN-γ, or towards the alternative M2a type by IL-4. M2b MØs are induced upon combined exposure to immune complexes and Toll-like receptor (TLR) ligands or IL-1 receptor agonists. M2c MØs are induced by IL-10 and glucocorticoids. Atheroprotective Mhem subset could be induced by hemoglobin, and highly express haem oxygenase 1 and CD163. Chemokine (C-X-C motif) ligand 4 drives differentiation of human specific M4 MØ, with unique expression of surface markers such as S100A8, mannose receptor CD206, and matrix metalloproteinase 7

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