| Title: |
TGFβ Receptor mutations alter mast cell development and function |
| Authors: |
Turfkruyer, Mathilde; Dugan, Philip A; Kinard, Jessica L; Frischmeyer-Guerrerio, Pamela |
| Source: |
The Journal of Immunology ; volume 198, issue Supplement_1, page 145.1-145.1 ; ISSN 0022-1767 1550-6606 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2017 |
| Description: |
Mutations in TGFBRI, encoding the receptor for TGFβ, cause Loeys-Dietz syndrome (LDS), a Mendelian disorder associated with an increased risk of developing nearly all forms of allergic disease, including food allergy. To better understand the mechanisms responsible for this association, knock-in mice harboring LDS mutations have been developed, which recapitulate nearly all aspects of the human phenotype. Mast cells are the main effector cells of allergic disease and several studies have identified TGFβ as a critical mediator of mast cell development and function. We hypothesized that LDS mast cells are altered in a manner that would promote greater susceptibility to allergic outcomes. To address this possibility, in vitro assays were performed with peritoneal mast cells (pMCs) cultured in IL-3 and stem cell factor and stimulated with IL-33, TGFβ, or IgE crosslinking agents. LDS pMCs expressed higher levels of ST2, the receptor for IL-33, and greater secretion of IL-9 following IL-33 stimulation. Furthermore, LDS pMCs were more resistant to apoptosis, exhibited greater degranulation following IgE receptor crosslinking, and showed less downregulation of FcɛRI and c-kit following exposure to recombinant TGFβ1. This was associated with reduced pSmad2/3 levels, a key signaling molecule in the TGFβ pathway. Furthermore, we demonstrated that following food allergy induction, LDS mice exhibited greater MC hyperplasia in the small intestinal lamina propria as well as in the peritoneum where LDS peritoneal mast cells showed enhanced secretion of IL-9. In vivo studies are ongoing to further examine the role of altered mast cell frequency and/or function resulting from altered TGFβ signaling in promoting food-induced anaphylaxis. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.4049/jimmunol.198.supp.145.1 |
| Availability: |
https://doi.org/10.4049/jimmunol.198.supp.145.1; https://academic.oup.com/jimmunol/article/198/Supplement_1/145.1/7970831 |
| Rights: |
https://academic.oup.com/pages/standard-publication-reuse-rights |
| Accession Number: |
edsbas.F3ABD25A |
| Database: |
BASE |