Specifically, E2 treatment upregulated interleukin 3-regulated nuclear factor (NFIL3
, GeneID 4783), nuclear receptor subfamily 1 group D member 1 (NR1D1, GeneID 9572), nuclear receptor subfamily 4 group A member 1 (NR4A1, GeneID 3164), while downregulated nuclear receptor subfamily 1 group I member 2 (NR1I2, GeneID 8856).
Moreover, MEL directly interferes with the differentiation of T cells, inducing the expression of the repressor transcription factor Nfil3
, blocking the differentiation of pathogenic Th17 cells and boosting the generation of protective Tr1 cells via Erk1/2 and the transactivation of the IL-10 promoter by ROR-[alpha] ; MEL inhibits also demyelination and increases remyelination .
The three genes with the largest change in expression were peroxisome proliferator activator receptor delta (Ppard), interleukin-3 regulated nuclear factor (Nfil3
), and nuclear receptor subfamily 1, group D, member 2 (Nr1d2); all of them are also linked with circadian rhythms .
Using a mouse model, the researchers identified a gene called Nfil3
, which guides the development of the TH17 cells that patrol mucosal surfaces like the intestinal lining and protect against bacterial and fungal infections.
Recently, E4BP4 (NFIL3
), a basic leucine zipper transcription factor, which was first recognized for its importance in NK cell development [116, 117], has been implicated in [CD8.sup.+] DC development.
This effect requires the IL-27-mediated induction of the nuclear factor, interleukin 3 regulated (NFIL3
), which mediates Tim-3 expression in vivo.
Markey et al., "CD8[[alpha].sup.+] DCs can be induced in the absence of transcription factors Id2, Nfil3
, and Batf3," Blood, vol.
In particular, studies in mice demonstrated the requirement of NFIL3
and Tbx21 (the gene encoding T-bet) for their development, while RORc (the gene encoding ROR[gamma]t) and aryl hydrocarbon receptor (AhR) were dispensable .