The Effect of Immunosuppressive Drugs on MDSCs in Transplantation

Table 2

Immunosuppressive drugs on MDSCs.

Class	Drugs	Years	Disease	MDSC subsets/expansion/function	Mechanism	In vitro induction	Ref.
CSs	Dex	2017	Immunological hepatic injury	Total/?/suppress T cell proliferation in MLR↑, production of TNFα↓, IL-10↑	GR↑ → HIF1↓ → glycolysis↓ → NO↑	—	[88]
	Dex	2014	Skin Tx	Total/spleen↑, graft↑/suppress T cell proliferation in MLR↑	GR → iNOS↑ → Th1 to Th2	—	[89]
	MP	2018	Intestinal Tx	M, PMN, e-MDSC/PMBC↑/suppress T to donor intestinal epithelial organoids	—	Gm-CSF + IL-6 + G-CSF + (MP)	[28]
	Dex	2018	Heart Tx	M-MDSC/BM induction↑/suppress T proliferation by ConA, CXCR2↑	GR↑ → iNOS↑	Gm-CSF + (Dex)	[90]
mTORi	Rapa	2014	Immunological hepatic injury	M-MDSC/liver↑/suppress T cell proliferation in MLR↑, CXCR2↑	iNOS↑ → recruitment to the liver↑	—	[111]
	Rapa	2014	Tumor in SIRT1 KO mice	Total/?/suppress T cell proliferation in MLR↑, production of NO↓, TNFα↓, Arg1↑, IL-10↑	Glycolysis↓	—	[113]
	Rapa	2015	Heart Tx	M, PMN-MDSC/spleen↑/suppress T cell proliferation by anti-CD3/28↑	iNOS↑, Arg1↑, Treg↑	—	[30]
	Rapa	2016	Skin Tx, tumor	M-MDSC/BM induction↓, spleen↓/suppress T cell proliferation by anti-CD3/28↓	Glycolysis↓, iNOS↓	Gm-CSF + (rapa)	[29]
	Rapa	2016	Immunological hepatic injury	Total/liver↑/suppress T cell proliferation in MLR↑, CXCR2↑	HIF1α↓, glycolysis↓, iNOS↑	Gm-CSF + (rapa)	[112]
	Rapa	2017	Immunological kidney injury	M, PMN-MDSC/spleen↑, kidney↑/suppress T cell proliferation by anti-CD3/28↑	Runx1↓ → iNOS↑, Arg1↑	Gm-CSF + IL-6 + (rapa)	[114]
CNIs	CsA	2014	Skin Tx	Total/spleen↑/suppress T cell proliferation in MLR↑, CXCR2↑, TNFα↓, IL-10↑, Th1 to Th2↑	NFAT↓ → IDO↑	—	[102]
	CsA	2016	Skin Tx	Total/spleen↑, BM induction↑/suppress T cell proliferation in MLR↑	iNOS↑	Gm-CSF + (CsA)	[103]
Costimulatory molecules	Anti-CD28	2008	Kidney Tx	Total/blood↑/suppress T cell proliferation in MLR↑	iNOS↑	—	[31]
	Anti-CD40L	2010	Heart Tx	M-MDSC/graft↑/suppress T cell proliferation by anti-CD3/28↑	IFN-γR → STAT1 → iNOS↑	—	[25]
	Anti-CD40L	2015	Heart Tx	MDSC-derived Mφ/graft ↑/suppress T cell proliferation in MLR↑	DC-SIGN, TLR-4 → IL-10↑	—	[42]