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Effect of MUC1 length polymorphisms on the NLRP3 inflammasome response of human macrophages

Version 2 2024-06-04, 14:31
Version 1 2019-06-27, 09:45
journal contribution
posted on 2024-06-04, 14:31 authored by Poshmaal DharPoshmaal Dhar, S Sarkar, GZ Ng, P Kalitsis, MA Saeed, MA McGuckin, JA Ellis, P Sutton
Mucin 1 is a cell-membrane associated mucin, expressed on epithelial and immune cells that helps protect against pathogenic infections. In humans, MUC1 is highly polymorphic, predominantly due to the presence of a variable number tandem repeat (VNTR) region in the extracellular domain that results in MUC1 molecules of typically either short or long length. A genetic link is known between these MUC1 polymorphisms and inflammation-driven diseases, although the mechanism is not fully understood. We previously showed that MUC1 on murine macrophages specifically restricts activation of the NLRP3 inflammasome, thereby repressing inflammation. This study evaluated the effect of MUC1 VNTR polymorphisms on activity of the NLRP3 inflammasome in human macrophages, finding that long MUC1 alleles correlated with increased IL-1β production following NLRP3 inflammasome activation. This indicates that the length of MUC1 can influence IL-1β production, thus providing the first evidence of an immune-modulatory role of MUC1 VNTR polymorphisms in human macrophages.

History

Journal

Human Immunology

Volume

80

Pagination

878-882

Location

United States

ISSN

0198-8859

eISSN

1879-1166

Language

English

Publication classification

C1 Refereed article in a scholarly journal

Copyright notice

2019, American Society for Histocompatibility and Immunogenetics

Issue

10

Publisher

ELSEVIER SCIENCE INC