Deletion of the ST2 proximal promoter disrupts fibroblast-specific expression but does not reduce the amount of soluble ST2 in circulation

European Journal of Immunology
Brian P LipskyDirke Smith

Abstract

IL-33 signals through ST2, which is expressed either as a full-length signaling receptor or a truncated soluble receptor that can suppress IL-33 activity. Previous data suggest that soluble ST2 mRNA in fibroblasts is coupled to a serum-inducible proximal promoter, while full-length ST2 expression in immune cells is directed from a distal promoter. In order to better understand the function of the alternative promoters and how they ultimately affect the regulation of IL-33, we generated a mouse in which the ST2 proximal promoter is deleted. Promoter deletion had no impact on ST2 expression in mast cells or their ability to respond to IL-33. In contrast, it resulted in a complete loss of both soluble and full-length ST2 mRNA in fibroblasts, which corresponded with both an inability to secrete soluble ST2 and a defect in IL-33 responsiveness. Importantly, in spite of the fibroblast defect, soluble ST2 concentrations were not reduced in the serum of naïve or allergen-exposed knockout mice. In summary, we found that ST2 promoter usage is largely cell-type dependent but does not dictate splicing. Moreover, the proximal promoter is not a major driver of circulating soluble ST2 under the conditions tested.

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Citations

Jan 18, 2013·Arthritis Research & Therapy·Praxedis MartinGaby Palmer
Sep 4, 2013·The Journal of Clinical Investigation·Jennifer E HoThomas J Wang
Dec 15, 2015·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·L R MathewsH R Turnquist
Nov 24, 2012·Pediatric Allergy and Immunology : Official Publication of the European Society of Pediatric Allergy and Immunology·Mirjam E BelderbosLouis Bont
Feb 13, 2015·Frontiers in Immunology·Abdulraouf Ramadan, Sophie Paczesny
May 28, 2016·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·B M MattaH R Turnquist
Aug 16, 2016·Seminars in Cell & Developmental Biology·Neal L MillarElizabeth Brint
Oct 26, 2016·Developmental and Comparative Immunology·Alexander ReblHans-Martin Seyfert

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