Table 1.

Summary of the effects of PM and AHR agonists on autoimmunity.

		Treatment	Immunosuppressive	Immunostimulatory	No effect on autoimmunity
Pre-clinical	PM	DEP PM		(100)
		DEP OF	(100)	(100)
		Ambient PM	(101)	(63, 64)
		Ambient OF
	AHR agonists	TCDD	(46, 102, 103)	(104–106)
		FICZ	(102)	(46, 106, 107)
		10-Cl-BBQ	(108)
		Norisoboldine	(109)
		Tetrandrine	(110)
		Sinomenine	(111)
		Laquinimod	(112)
		ITE	(113)
		I3C	(107, 114)
		DIM	(107, 114)
	AHR knockout		(115–117)
Clinical	PM			(16, 18–21, 23, 27, 59, 71, 72, 76, 78, 81–86, 90, 92)	(70, 71, 73, 79, 80, 83, 85, 95–97)
	AHR antagonists	GNF351	(118, 119)

This table summarizes the effects of PM and other AHR ligands in preclinical and clinical studies based on whether the treatment led to an immunosuppressive or immunostimulatory outcome. Preclinical studies include in vivo animal studies whereas the clinical studies include epidemiology studies as well as studies using human cells or tissue. Most of the studies using AHR agonists led to an immunosuppressive effect whereas PM had both immunosuppressive and immunostimulatory effects. Route of exposure and extent and duration of AHR activation contribute to the effects of AHR ligands on autoimmunity and may explain the differential responses observed in these studies. Several clinical epidemiology data suggest that PM exposure leads to immunostimulatory responses while some suggest it does not have an effect on autoimmunity. Together, these data led to the novel hypothesis that PAHs adhered to PM activate the AHR, shift the T cell balance, and lead to PM-mediated autoimmune disease.