. 2019 Mar 6;20(5):1142. doi: 10.3390/ijms20051142

Table 1.

Modulation of regulatory T (Treg) cell subsets following GC treatment in healthy animals and disease models.

Paper	Species (Strain)	Disease	Drug, Dose, and Days of treatment		Time Elapsed from the Last Treatment	Evaluated Tissue	Treg Population	Modulation of the Treg Subset (Significance) ¹
Boivin et al. 2018 [121]	Horse (N.A.)	No disease	14 day treatment with dexamethasone,.06 mg/Kg per day		on treatment	Bronchoalveolar lavage fluid	% FoxP3⁺ in CD4⁺ T cells	= vs. baseline
Chen et al. 2004 [101]	Mouse (BALB/c)	No disease	1 day treatment with dexamethasone, i.p., 5 mg/Kg		1 day after the injection	Thymus	CD4⁺CD25⁺ absolute number	↑(*) vs. untreated controls
						Thymus	CD4⁺CD25⁺/CD4⁺CD25⁻ ratio	↑(**) vs. untreated controls
						Spleen	CD4⁺CD25⁺/CD4⁺CD25⁻ ratio	↑(**) vs. untreated controls
					3 days after the injection	Thymus	CD4⁺CD25⁺ absolute number	↑(*) vs. untreated controls
					3 days after the injection	Thymus	CD4⁺CD25⁺/CD4⁺CD25⁻ ratio	↑(*) vs. untreated controls
			1, 3 and 5 day treatment with dexamethasone, i.p., 5 mg/Kg per day		1 day after the first injection	Thymus	CD4⁺CD25⁺ absolute number	↑(*) vs. untreated controls
					1 day after the first injection	Thymus	CD4⁺CD25⁺/CD4⁺CD25⁻ ratio	↑(*) vs. untreated controls
					1 day after the fifth injection	Thymus	CD4⁺CD25⁺ absolute number	↑(**) vs. untreated controls
					1 day after the fifth injection	Thymus	CD4⁺CD25⁺/CD4⁺CD25⁻ ratio	↑(**) vs. untreated controls
			3 day treatment with dexamethasone, i.p., 5 mg/Kg per day		1 day after the last injection	Thymus	CD4⁺CD8⁻CD25⁺ absolute number	↑(**) vs. untreated controls
						Spleen		↑(*) vs. untreated controls
						Lymph nodes		↑(*) vs. untreated controls
Chen et al. 2006 [120]	Mouse (BALB/c)	No disease	1–5 day treatment with dexamethasone, i.p., 5 mg/Kg per day plus IL-2 300 000 IU per day		1 day after the last injection	Spleen, lymph nodes	% CD25⁺ in CD4⁺ T cells	↑(**) vs. untreated controls
			3 day treatment with dexamethasone, i.p., 5 mg/Kg per day		1 day after the last injection	Spleen	CD4⁺CD25⁺/CD4⁺CD25⁻ ratio	↑(**) vs. untreated controls
						Spleen	CD4⁺CD25⁺ absolute number	↓(*) vs. untreated controls
						Lymph nodes, spleen, blood	% CD4⁺FoxP3⁺ in all cells	↓(N.A.) vs. untreated controls
			3 day treatment with dexamethasone, i.p., 5 mg/Kg per day plus IL-2 300 000 IU per day		1 day after the last injection	Spleen	CD4⁺CD25⁺/CD4⁺CD25⁻ ratio	↑(**) vs. untreated controls
							CD4⁺CD25⁺ absolute number	↑(**) vs. untreated controls
							% CD4⁺FoxP3⁺ in all cells	↑(N.A.) vs. untreated controls
						Lymph nodes, blood	% CD4⁺FoxP3⁺ in all cells	↑(N.A.) vs. untreated controls
						Lymph nodes, spleen, blood	% FoxP3⁺ in CD3⁺CD4⁺ T cells	↑(N.A.) vs. untreated controls
					3 days after the last injection	Lymph nodes, spleen, blood	% FoxP3⁺ in CD3⁺CD4⁺ T cells	↓(N.A.) vs. untreated controls
					21 days after the last injection	Lymph nodes, spleen, blood	% FoxP3⁺ in CD3⁺CD4⁺ T cells	↑(N.A.) vs. untreated controls
Chen et al. 2018 [117]	Mouse (C57BL/6)	No disease	3 day treatment with dexamethasone, i.p. 0.1 or 100 μg per day		2 days after the last injection	Spleen	CD4⁺CD25⁺ absolute number	↑() or ↑ (**) (0.1, 100μg respectively) vs. untreated control
Sbiera et al.2011 [119]	Mouse (C57Bl/6)	No disease	3 day treatment with dexamethasone, i.p., 0.8 mg/Kg per day (similar results with 4, 20, 100 mg/Kg per day)		After treatment	Spleen, blood	CD4⁺CD25^highFoxP3⁺ absolute number	↓(N.A.) vs. untreated controls
Sbiera et al.2011 [119]	Mouse (C57Bl/6)	No disease			After treatment	Spleen, blood	% CD25^highFoxP3⁺ in CD4⁺ T cells	↓(N.A.) vs. untreated controls
Zuska-Prot et al. 2017 [123]	Mouse (BALB/c)	No disease	9 day treatment with methylprednisolone (MP), i.m., 2 mg/Kg per day or 9 day treatment with Ciclesonide (CIC), inhaled, 160 μg per day		1 day after the last treatment	Lung	CD4⁺CD25⁺FoxP3⁺ absolute number	CIC↓(***) vs. untreated controls
						mediastinal lymph nodes		CIC↓(*) vs. untreated controls MP ↓(*) vs. untreated controls
						head and neck lymph nodes		CIC↓(*) vs. untreated controls MP ↓(*) vs. untreated controls
						blood		CIC↓(**) vs. untreated controls MP↓() vs. untreated controls
Ugor et al. 2018 [118]	Mouse (BALB/c)	No disease	1-4 day treatment with dexamethasone, i.p., 20 mg/Kg per day		1 day after the last injection	thymus	% CD25⁺FoxP3⁺ in CD4⁺ T cells	↑(N.A.) at day 1 vs. untreated controls (same result at day 2 and 4)
			1 day treatment with dexamethasone, i.p., 20 mg/Kg per day		4 or 8 h after the injection	blood	% CD25⁺FoxP3⁺ in CD4⁺ T cells	↑(*) vs. untreated controls
			4 day treatment with dexamethasone, i.p., 20 mg/Kg per day		1 day after the last injection	thymus	CD4⁺CD25⁺FoxP3⁺ absolute number	= vs. untreated controls
						spleen		↓(**) vs. untreated controls
						lymph nodes		↓(***) vs. untreated controls
						peyer’s patches		↓(*) vs. untreated controls
Kawalkowska et al. 2016 [124]	Mouse (DBA/1)	Arthritis	10 day treatment with dexamethasone, i.p., 160 μg per dayplus IL-4, i.p., on day 1, 4, and 7 post disease onset		on treatment	joints of paw	% CD25⁺FoxP3⁺ in CD4⁺ T cells	↑(**** vs. untreated controls) ↑(* vs. mice treated with Dex alone)
					on treatment	joints of paw	Th17/Tregs ratio	↓(* vs. untreated controls) ↓(** vs. mice treated with Dex alone)
					11 days after the last treatment	joints of paw	Th17/Tregs ratio
Boivin et al. 2018 [121]	Horse (N.A.)	Severe asthma	14 day treatment with dexamethasone, 0.06 mg/Kg per day		on treatment	bronchoalveolar lavage fluid	% FoxP3⁺ in CD4⁺ T cells	↑(*** vs. healthy controls) ↑(* vs. baseline)
Olsen et al. 2015 [125]	Mouse (A/J)	Asthma (sensitization and first OVA challenges)	• (protocol 1) treatment with dexamethasone, os, 1 mg/Kg, same days of challenge (3 days/week during 3 weeks) • (protocol 2) treatment with dexamethasone, os, 1 mg/Kg per day, (on the last week of challenge) • (protocol 3) treatment with budesonide, nebulized, 7.5 mg/mL, same days as protocol 2, 3 (inhalation cycles of 10 min each) • (protocol 4) treatment with budesonide, nebulized, 7.5 mg/mL, same days as protocol 2, 3 (inhalation cycles of 30 min each)	protocol 1, protocol 2, and protocol 3	1 day after the last treatment	bronchoalveolar lavage fluid	CD4⁺CD25⁺FoxP3⁺ absolute number	↓(*) vs. untreated mice
				protocol 1, protocol 2, and protocol 3	1 day after the last treatment	lung
				protocol 1	7 days after the last treatment	bronchoalveolar lavage fluid
				protocol 1, protocol 2, and protocol 3	1 day after the last treatment	lymph node
				protocol 2, and protocol 3	1 day after the last treatment	thymus
				protocol 2 and protocol 4	1 day after the last treatment	airways and lung	CD4⁺CD25⁺FoxP3⁺ absolute number	↓(*) vs. untreated mice
	Mouse (BALB/c)	Asthma (HDM challenges)		protocol 2 and protocol 4	1 day after the last treatment	airways and lung	CD4⁺CD25⁺FoxP3⁺ absolute number	↓(*) vs. untreated mice
Wu et al. 2016 [126]	Mouse (BALB/c)	Asthma (sensitization and first OVA challenges)	3 day treatment with dexamethasone, ranging from 12.5 to 18.75 μg/day plus IL-2, intratracheal, ranging from 50000 to 75000 IU per day		1 day after the last treatment	bronchoalveolar lavage fluid	CD4⁺CD25⁺ absolute number	↑(*) vs. untreated asthmatic mice
Zou et al. 2017 [127]	Mouse (BALB/c)	Asthma (sensitization and first OVA challenges)	7 day treatment with dexamethasone, i.p., 1 mg/kg per day		N.A.	bronchoalveolar lavage fluid	% CD25⁺FoxP3⁺ in CD4⁺ T cells	↓(**) vs. healthy controls ↑(N.A.) vs. asthmatic untreated mice
Zou et al. 2017 [127]	Mouse (BALB/c)	Asthma (sensitization and first OVA challenges)	7 day treatment with dexamethasone, i.p., 1 mg/kg per day		N.A.	pulmonary tissue	FoxP3 expression (evaluated by q-PCR, IHC, and SDS-PAGE)	↓(**) vs. healthy controls ↑(N.A.) vs. asthmatic untreated mice
Zuska-Prot et al. 2017 [123]	Mouse (BALB/c)	asthma (sensitization and first OVA challenges)	treatment with Ciclesonide (CIC), inhaled, 160 μg/mouse per day or treatment with methylprednisolone (MP), i.m., 2 mg/kg per day	4 days of treatment	on treatment	lung	CD4⁺CD25⁺FoxP3⁺ absolute number	OVA+CIC↓(*) vs. untreated controls OVA+MP↓() vs. untreated controls
				4 days of treatment	on treatment	Mediastinal lymph nodes	CD4⁺CD25⁺FoxP3⁺ absolute number	OVA+CIC↓(*) vs. untreated controls and healthy controls
				9 days of treatment	on treatment	lung	CD4⁺CD25⁺FoxP3⁺ absolute number	OVA+CIC↓(*) vs. untreated controls OVA+MP↓() vs. untreated controls
						mediastinal lymph nodes		OVA+CIC↓(**) vs. untreated controls OVA+MP↓() vs. untreated controls
						head and neck lymph nodes		OVA+CIC↓(*) vs. untreated controls and healthy controls OVA+MP↓(*) vs. untreated controls and healthy controls
						peripheral blood		OVA+CIC↓(*) vs. healthy controls OVA+MP↓(*) vs. healthy controls
				23 days of treatment	on treatment	lung	CD4⁺CD25⁺FoxP3⁺ absolute number	OVA+CIC↓(*) vs. untreated controls OVA+MP↓(*) vs. untreated controls
						mediastinal lymph nodes		OVA+CIC↓(*) vs. healthy controls and untreated controls OVA+MP↓(*) vs. healthy controls and untreated controls
						head and neck lymph nodes		OVA+CIC↓(*) vs. untreated controls and healthy controls OVA+MP↓(*) vs. healthy controls
						peripheral blood		OVA+CIC↓(*) vs. healthy controls and untreated controls OVA+MP↓(*) vs. healthy controls and untreated controls
Boivin et al. 2018 [121]	Horse (N.A.)	severe asthma	14 day treatment with dexamethasone, 0.06 mg/Kg per day		on treatment	bronchoalveolar lavage fluid	% FoxP3⁺ in CD4⁺ T cells	↑(*** vs. healthy controls) ↑(* vs. baseline)
Chen et al. 2014 [128]	Mouse (APOE^−/− C57BL/6)	atherosclerosis	3 day treatment with dexamethasone, i.m., 4.5 mg/Kg on day 1, 2.25 mg/Kg on day 2 and 3		14 days after the last treatment	spleen	% FoxP3⁺ in CD4⁺ T cells	↑(*) vs. untreated controls
Nakao et al. 2018 [116]	Mouse (B6N)	cardiac graft	6 day treatment with dexamethasone, i.p., 5 mg/Kg on day 0,2,4, and 6)		4 days after the last treatment	spleen	% FoxP3⁺ in CD3⁺CD4⁺	↑(*) vs. untreated controls
							% FoxP3⁺ in splenocytes	↑(***) vs. untreated controls
			6 day treatment with dexamethasone, i.p., 5 mg/Kg on day 0,2,4, and 6), plus anti-Gr-1 Ab, i.p., on postoperative days 1 and 4				% FoxP3⁺ in CD3⁺CD4⁺	↓(***) vs. mice treated with dexamethasone alone
							% FoxP3⁺ in splenocytes	↓(***) vs. mice treated with dexamethasone alone
You et al. 2018 [129]	Mouse (BALB/c)	colitis	4 day treatment with dexamethasone, orogastric gavage, 5 mg/Kg per day, plus AdTGF²		N.A.	mesenteric lymph nodes	FoxP3 expression (q-PCR)	↑(**) vs. mice treated with AdTGF-1 alone
You et al. 2018 [129]	Mouse (BALB/c)	colitis			N.A.	mesenteric lymph nodes	FoxP3⁺ absolute number	↑(**) vs. mice treated with AdTGF-1 alone
Zhang et al. 2013 [130]	Mouse (NOD)	type I diabetes	(14-days protocol) treatment with dexamethasone in the two hind footpads, 16 mg/Kg on days 1, 4, 7, 10, plus injection of insuline peptide (B9-23) co-injected at day-7		7 days after the last treatment	spleen	% CD25⁺FoxP3⁺ in CD4⁺ T cells	↑(*) vs. untreated controls, mice treated with dexamethasone alone and insuline peptide alone
					7 days after the last treatment		% FoxP3⁺IL-10⁺ in CD4⁺CD25⁺ T cells
					45 days after the last treatment		% CD44⁺CD62L⁻ in CD4⁺FoxP3⁺ T cells	↑(*) vs. mice treated with insulin peptide
Chen et al. 2006 [120]	Mouse (C57BL/6)	experimental autoimmune encephalomyelitis (EAE)	3 day prior to immunization treatment with dexamethasone, i.p., 5 mg/Kg plus IL-2, i.v., 4 μg		N.A.	spleen	% FoxP3⁺ in CD4⁺ T Cells	↑(N.A.) vs. untreated EAE mice
Wüst et al. 2008 [131]	mouse ³ (C57BL/6 Gr^flox)	experimental autoimmune encephalomyelitis (EAE)	3 day treatment with dexamethasone, i.p., 100 mg/Kg per day		58 h after the last treatment	spleen	% FoxP3⁺GITR⁺ in CD4⁺ Tcells	↓(N.A.) vs. untreated controls
	mouse ³ (C57BL/6 Gr^flox)						MFI of FoxP3	↓(**) vs. untreated controls
	mouse ³ (C57BL/6 Gr^lck)						% FoxP3⁺GITR⁺ in CD4⁺ T cells	↓(N.A.) vs. untreated controls
	mouse ³ (C57BL/6 Gr^lck)						MFI of FoxP3	= vs. untreated controls

¹ ↑, increase; (*) p < 0.05, (**) p < 0.01, (***) p < 0.001, (****) p < 0.0001, (N.A.), not available; ↓, decrease; (*) p < 0.05, (**) p < 0.01, (***) p < 0.001, ( N.A.) not available; ² adenovirus expressing TGF-β; ³ GR^lck mice, the T cells of these mice do not express the glucocorticoid receptor; Gr^flox, control mice.