Death receptor 3 regulates distinct pathological attributes of acute versus chronic murine allergic lung inflammation

Singh, Ravinder, Perks, William, Twohig, Jason, Kidd, Emma ORCID: https://orcid.org/0000-0001-5507-1170, Broadley, Kenneth ORCID: https://orcid.org/0000-0002-3339-2050, Farrow, S N, Williams, Anwen ORCID: https://orcid.org/0000-0001-6118-020X, Taylor, Philip ORCID: https://orcid.org/0000-0003-0163-1421 and Wang, Edward ORCID: https://orcid.org/0000-0002-2243-4964 2017. Death receptor 3 regulates distinct pathological attributes of acute versus chronic murine allergic lung inflammation. Cellular Immunology 320 , pp. 62-70. 10.1016/j.cellimm.2017.09.005

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Abstract

The Death Receptor 3 (DR3)/Tumour Necrosis Factor-like cytokine 1A (TL1A) axis stimulates effector T cells and type 2 innate lymphocytes (ILC2) that trigger cytokine release and drive disease pathology in several inflammatory and autoimmune diseases, including murine models of acute allergic lung inflammation (ALI). The aim of this study was to elucidate the role of DR3 in chronic ALI compared to acute ALI, using mice genetically deficient in the DR3 gene (DR3ko). Results showed DR3 expression in the lungs of wild-type mice was up-regulated following induction of acute ALI and this increased expression was maintained in chronic disease. DR3ko mice were resistant to cellular accumulation within the alveolar passages in acute, but not chronic ALI. However, DR3ko mice displayed reduced immuno-histopathology and goblet cell hyperplasia; hallmarks of the asthmatic phenotype; in chronic, but not acute ALI. These data suggest DR3 is a potential therapeutic target, involved in temporally distinct aspects of ALI progression and pathogenesis.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Pharmacy
Subjects:	R Medicine > R Medicine (General) R Medicine > RM Therapeutics. Pharmacology
Publisher:	Elsevier
ISSN:	0008-8749
Funders:	BBSRC, MRC
Date of First Compliant Deposit:	21 September 2017
Date of Acceptance:	11 September 2017
Last Modified:	10 Feb 2024 02:11
URI:	https://orca.cardiff.ac.uk/id/eprint/104922

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