Given an abstract from a research paper, your task is to identify and label relationships between chemical compounds and genes mentioned in the abstract.

The relationship type must be one of ['DOWNREGULATOR', 'SUBSTRATE', 'INDIRECT-REGULATOR', 'PART-OF', 'MODULATOR-ACTIVATOR', 'REGULATOR', 'INHIBITOR', 'COFACTOR', 'UPREGULATOR', 'ACTIVATOR', 'ANTAGONIST', 'NOT', 'INDIRECT-DOWNREGULATOR', 'SUBSTRATE_PRODUCT-OF', 'INDIRECT-UPREGULATOR', 'AGONIST', 'PRODUCT-OF', 'MODULATOR', 'DIRECT-REGULATOR', 'UNDEFINED', 'AGONIST-INHIBITOR', 'AGONIST-ACTIVATOR', 'MODULATOR-INHIBITOR'].

Please format your output as a JSON array. Each entry in the array should express a single relation, formatted as ["<Entity_A>", "<RELATION_A_B>", "<Entity_B>"]. If no relations can be found, please output an empty JSON array [].

Abstract:

Indoxyl 3-sulfate stimulates Th17 differentiation enhancing phosphorylation of c-Src and STAT3 to worsen experimental autoimmune encephalomyelitis. Although AhR activation regulates CD4 T cell differentiation, how it works has yet to be elucidated. In the present study, using in vitro Th17 differentiation model, we examined effects of AhR activation by indoxyl 3-sulfate (I3S), a uremic toxin, on Th17 differentiation and investigated underlying mechanisms. I3S increased expression of RORγt, the master transcription factor for Th17 differentiation, and stimulated Th17 differentiation, in a comparative manner as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a prototypical AhR ligand. Activation of STAT3, which is phosphorylated by the IL-6 signaling pathways and thus is necessary for Th17 differentiation, was strongly stimulated by I3S and TCDD. Phosphorylation of c-Src, which was shown to be activated by AhR ligands, was also increased by I3S and TCDD, and blocking of c-Src activity by 4-amino-5- (4-chlorophenyl) -7- (t-butyl) pyrazolo[3,4-d]pyrimidine (PP2) inhibited phosphorylation of both c-Src and STAT3, raising a possibility that stimulatory activities of I3S and TCDD on Th17 differentiation could be exerted via increased phosphorylation of c-Src, which in turn stimulates STAT3 activation. Finally, we found that I3S worsened experimental autoimmune encephalomyelitis (EAE), which is primarily mediated by Th17 cells, enhancing the frequency of IL-17-producing cells in draining lymph nodes.
[["4-amino-5- (4-chlorophenyl) -7- (t-butyl) pyrazolo[3,4-d]pyrimidine", "INHIBITOR", "c-Src"], ["I3S", "ACTIVATOR", "STAT3"], ["I3S", "REGULATOR", "AhR"], ["TCDD", "ACTIVATOR", "IL-6"], ["TCDD", "REGULATOR", "AhR"], ["I3S", "ACTIVATOR", "c-Src"], ["I3S", "ACTIVATOR", "AhR"], ["Indoxyl 3-sulfate", "ACTIVATOR", "c-Src"], ["indoxyl 3-sulfate", "ACTIVATOR", "AhR"], ["Indoxyl 3-sulfate", "ACTIVATOR", "STAT3"], ["TCDD", "DIRECT-REGULATOR", "AhR"], ["I3S", "INDIRECT-UPREGULATOR", "ROR\u03b3t"], ["I3S", "ACTIVATOR", "IL-6"], ["TCDD", "ACTIVATOR", "c-Src"], ["2,3,7,8-tetrachlorodibenzo-p-dioxin", "DIRECT-REGULATOR", "AhR"], ["TCDD", "ACTIVATOR", "STAT3"], ["4-amino-5- (4-chlorophenyl) -7- (t-butyl) pyrazolo[3,4-d]pyrimidine", "INHIBITOR", "STAT3"]]