Inflammatory niche: Mesenchymal stromal cell priming by soluble mediators

Table 1 Influence of inflammatory priming on immunomodulatory features of mesenchymal stromal/stem cells under in vitro conditions

	Priming factor	MSCs source	Immunomodulatory effects of inflammatory priming	Suggested mechanism	Ref.
Pro-inflammatory cytokines	IFN-γ	hWJ-MSCs	↓ Th1 and Th17 cells proliferation	↑ CXCL9, CXCL10, CXCL11, ICAM-1, VCAM-1, IDO1 and HLA-G5 gene expression	Wang et al[35], 2016
			↑ Th2 and Tregs (CD4+, CD25+, CD127dim/− cells) percentage	↓ IFNγ, TNFα but ↑ IL-10 and IL-6 secretion in co-culture with PB-MNCs
		hBM-MSCs	↓ T-cell effector functions and Th1 cytokine (IFN-γ, TNF-α, and IL-2) production	↑ B7H1 and B7DC (ligands for PD1) expression	Chinnadurai et al[36], 2014
	IFN-γ and TNF-α	hBM-MSCs	↓ T cell proliferation	↑ IDO activity	François et al[55], 2012
			↑ Monocyte differentiation into M2 (IL-10-secreting CD206+) immunosuppressive macrophages
			↓ CD3/CD28-induced T-cell proliferation	↓ Potency to trigger increased IFN-γ and IL-2 synthesis by activated T cells	Cuerquis et al[59], 2014
	TNF-α/IFN-γ and IL-β	rBM-MSCs	↓ Proliferation of syngeneic lymphocytes	↑ NO production	Murphy et al[80], 2019
	IL-17	hBM-MSCs	↓ PHA-stimulated T-cell proliferation	↑ IL-6 gene expression	Sivanathan et al[94], 2015
			↓ Expression of CD25 on CD4+ effector T cells	Treg-mediated IL-2 deprivation
			↓ T cell effector function and Th1 cytokines (IFN-γ, TNF-α, IL-2) secretion
			↑ Formation of Tregs (CD4+ CD25 high CD127 low FoxP3+)	Cell-contacts and ↑ PGE2 and TGF-β expression
	IFN-γ, TNF-α and IL-17	mBM-MSC	↓ T-cell proliferation	↑ iNOS expression	Han et al [95], 2014
	IFN-γ, TNF-α and IL-6	hAT-MSC	↓ Proliferation of PHA or MLR activated PB-MNCs	↑ IDO expression	Crop et al[111], 2010
Alarmins	IL-1α	hBM-MSCs	↓ IL-6, TNF-α and ↑ IL-10 secretion in LPS-activated mouse microglial BV2 cells	↑ G-CSF secretion	Redondo-Castro et al[78], 2017
	HMGB1	hBM-MSC	Unaffected inhibition of Con A-induced lymphocyte proliferation	/	Meng et al[118], 2008

Symbols: ↑ and ↓ represent stimulatory or inhibitory activity of priming factor, respectively. IFN-γ: Interferon gamma; TNF-α: Tumor Necrosis Factor alpha; IL: Interleukin; HMGB1: High mobility group box 1; MSCs: Mesenchymal stromal/stem cells; h: Human; WJ: Warthon jelly’s; BM: Bone marrow; r:rat; AT: Adipose tissue; Th: T helper; PHA: Phytohaemagglutinin; MLR: Mixed lymphocyte reaction; LPS: Lipopolysaccharide; Con A: Concanavalin A; CXCL: C-X-C motif chemokine ligand; ICAM-1: Intercellular adhesion molecule-1; VCAM-1: Vascular cell adhesion molecule 1; IDO: Indoleamine-pyrrole 2,3-dioxygenase; HLA-G5: Human leukocyte antigen-G molecules; PB-MNCs: Peripheral blood mononuclear cells; B7H1: B7 homolog 1; PD1: Programmed cell death protein 1; NO: Nitric oxide; PGE2: Prostaglandin E₂; TGF-β: Transforming growth factor beta; iNOS: Inducible NO synthase; G-CSF: Granulocyte - colony stimulating factor.