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Mayumi Ueta, Hiromi Nishigaki, Kiyoko Oosako, Shigeru Kinoshita; Regulation of Ikzf1 inducible genes by TLR3 and IPS-1. Invest. Ophthalmol. Vis. Sci. 2018;59(9):141. doi: https://doi.org/.
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Our previous genome-wide association study documented an association between cold medicine related Stevens-Johnson syndrome / toxic epidermal necrolysis (CM-SJS/TEN) and Ikaros Family Zinc Finger 1 (IKZF1). We also reported that human epidermis and conjunctival epithelium expressed IKZF1, and in primary human conjunctival epithelial cells and adult human epidermal keratinocytes, the expression of IKZF1 mRNA was up-regulated by stimulation with polyI:C, a TLR3 ligand, We also generated K5-Ikzf1-EGFP transgenic mice (Ikzf1 Tg) by introducing the Ik1 isoform into cells expressing keratin 5, which is expressed in epithelial tissues such as the epidermis and conjunctiva and found that Ikzf1 Tg mice have dermatitis and mucosal inflammation including the ocular surface. In this study, we investigated the difference in gene expression in the epidermis of Tg and WT mice, and the regulation of the Ikzf1 inducible genes by TLR3 and IPS-1, which are receptors for polyI:C.
Skin was collected from the mice which are within 1 week after their birth, and epidermis was harvested from the skin using dispase. We compared the gene expression of the epidermis between Ikzf1 Tg mice and WT mice using microarray. Moreover, using TLR3KO, Ikzf1Tg TLR3KO, IPS-1KO, and Ikzf1Tg IPS-1KO mice, we investigated the regulation of Ikzf1 inducible genes by TLR3 and IPS-1 with quantitative RT-PCR.
Microarray analysis showed that Lcn2, Adh7, Epgn, Ifi202b, Cdo1, Gpr37, Duoxa1, Tnfrsf4, and Enpp5 genes were significantly up-regulated in the epidermis of Ikzf1 Tg compared with wild-type. Ikzf1 gene expression in the Ikzf1 Tg was significantly downregulated in Ikzf1Tg TLR3KO mice. Ifi202b, Gpr37 and Tnfrsf4gene expression in the Ikzf1 Tg were significantly down-regulated in both Ikzf1Tg TLR3KO and Ikzf1Tg IPS-1KO mice. Adh7 gene expression in the Ikzf1 Tg was significantly up-regulated in Ikzf1Tg TLR3KO but not in Ikzf1Tg IPS-1KO mice.
These findings suggest that Ikzf1 inducible genes could be partially controlled by TLR3 and IPS-1.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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