In:
The Journal of Immunology, The American Association of Immunologists, Vol. 200, No. 1_Supplement ( 2018-05-01), p. 44.17-44.17
Kurzfassung:
Allergic asthma affects more than 300 million people worldwide and is characterized by airway hypersensitivity and eosinophilia. A prevalent feature of allergic asthma is increased serum IL-33 levels, and asthma GWAS have demonstrated that SNPs in the IL-33 locus are significantly associated with disease. While IL-33 and its downstream type 2 responses have been extensively studied in murine models of asthma, much less is known about the regulation of human IL33. Analysis of the mouse and human IL33 loci reveals little genomic conservation between the two species in non-coding regions. We generated a novel BAC transgenic mouse strain containing the human IL-33 locus with a fluorescent reporter to interrogate the regulation and expression of human IL-33. Surprisingly, the mice expressed human IL-33 primarily in endothelial cells, whereas murine IL-33 was expressed primarily in epithelial cells. These results mirror the expression profiles of IL-33 in primary human lung cells from the LungGENS database, thus demonstrating that our novel mouse model faithfully replicates human IL-33 expression. To understand how human IL-33 in the lung is regulated and expressed during inflammation, we examined BAC transgenic mice challenged with either house dust mite extract (HDM) or poly(I:C). In contrast to murine IL-33, expression of human IL-33 was reduced during allergic inflammation. We tested whether IL-33 is able to autoregulate itself via a negative feedback loop. Indeed, IL-33 administration downregulated the expression of human IL-33 in lung endothelial cells. Together, these data emphasize a distinct and novel role in humans for lung endothelial cells in allergic airway disease by producing and responding to IL-33.
Materialart:
Online-Ressource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.200.Supp.44.17
Sprache:
Englisch
Verlag:
The American Association of Immunologists
Publikationsdatum:
2018
ZDB Id:
1475085-5
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