TABLE 4.

Diversity of immune effects by phthalate EDCs.

	Dose (μg/L)	Species	Cell type	Immune impact
In vitro
MBP	22,200 (Hansen et al., 2015)	Human	T Cells	↑	IL-6
MEHP	20 (Li et al., 2018)	Mouse (F)	M Φ	↓	Phagocytosis
DEP	22,200 (Hansen et al., 2015)	Human	M Φ	↑	IL-6
				↑	CXCL8
				↑	IL-10
				↓	TNF-α
			T Cells	↓	IL-2
				↓	IL-4
				↓	TNF-α
				↓	IFN-γ
DBP	27,800 (Hansen et al., 2015)	Human	MΦ	↑	IL-6
				↑	CXCL8
				↑	IL-10
				↓	TNF-α
			T Cells	↓	IL-2
				↓	IL-4
				↓	TNF-α
				↓	IFN-γ
BBP	31a (Kuo et al., 2013)	Human	Plasmacytoid dendritic cells	↓	IFN-α
			T Cells	↑	IFN-β
				↓	IFN-γ
				↑	IL-13
DEHP	≥1,560 (Martins et al., 2015)	Rainbow trout	B Cells	↓	Proliferation
	≥6,250 (Martins et al., 2015)		IgM plasmablasts/Plasma cells	↓	Proliferation
	60 and 600 μg/kg/d (Li et al., 2018)	Mouse	MΦ	↓	TNF-α mRNA (F)
				↓	IL-1 mRNA (F)
				↑	IL-6 mRNA (F)
	3,900 (Ito et al., 2012)		Dendritic cells	↑	Differentiation and maturity
	30, 300, 3,000 μg/kg (Han et al., 2019)		TFH	↑	Bcl-6
				↑	c-MAF
				↑	IL-21
				↑	IL-4
	39a (Kuo et al., 2013)	Human	Plasmacytoid dendritic cells	↓	IFN-α
				↑	IFN-β
			T Cells	↓	IFN-γ
				↑	IL-13
In vivo
BBP	3,000 (Elter et al., 2020)	Mouse	N/A	↑	Severity of RA in progeny
			Serum	↑	IgG1
				↑	IgG2a
			Splenocytes	↑	IFN-γ
				↑	IL-17
DEHP	60 and 600 μg/kg/d (Li et al., 2018)	Mouse	MΦ	↓	TNF-α gene expression
	60 μg/kg/d (Li et al., 2018)			↓	Phagocytosis
	30, 300, 3,000 μg/kg (Han et al., 2014)		TFH	↑	Co-stimulatory activity
				↑	SLAMF1 and SAP
				↑	Germinal center formation
	11.3–13.3 mg/kg/d (Hirai et al., 2015)	Mouse (M with EAO)	MΦ and other cells	↑	Number IFN-γ+
			Lymphocytes	↑	Infiltrates
			Serum	↑	Anti-testicular germ cell autoantibodies

^aImmune effect at high dose(s) only; (F), female bias; (M), male bias; MBP, monobutyl phthalate; MEHP, mono-(2-ethylhexyl) phthalate; DEP, diethyl phthalate; DBP, dibutyl phthalate; BBP, butyl benzyl phthalate; DEHP, di (2-ethylhexyl) phthalate; TFH, follicular helper T cells.