School of Medicine

A team led by the University of Luebeck involving a group of Cardiff University researchers have uncovered a novel pathway for the regulation of inflammation that is published this week in Nature Medicine .

The pathway involves the unexpected collaboration of distinct immune molecules in the suppression of inflammation and hence identifies potential new therapeutic targets for the amelioration of inflammatory diseases. Specifically, this study links the myeloid cell expressed lectin, dectin-1, to the inhibitory receptor FcgRIIB and the suppression of inflammation by galactosylated immune complexes.

Dectin-1 is known best for its role in the activation of immune cells during fungal infection after recognition of fungal carbohydrates. In this study, the team show an unexpected link through which galactosylated IgG1 immune complexes require both the inhibitory receptor FcgRIIB and dectin-1 to suppress inflammatory responses mediated through the complement anaphylatoxin C5a via suppression of its receptor (C5aR/CD88). These discoveries were primarily made possible through the careful analysis of experimental mice with defined genetic alterations.

The Cardiff team, led by Prof Philip Taylor, helped with the mechanistic studies via the analysis of their dectin-1-deficient mouse model (Taylor et al., 2007. Nat Immunol. 8: 31-38) and the study of immune signalling. Amongst other studies, they were able to perform experiments only possible in a few laboratories in the world using genetically-modified in vitro-derived neutrophils (McDonald et al., 2011. FASEBJ. 25:1972-1982).

These cell systems were characterised within the laboratory as part of an Medical Research Council (MRC) doctoral training grant funded PhD studentship whose objective was to help replace the use of animals in neutrophil research. The Cardiff contribution to the study was underpinned by MRC Senior Fellowship funding (Taylor).