Chitinase-like proteins promote IL-17-mediated neutrophilia in a tradeoff between nematode killing and host damage

TE Sutherland, N Logan, D Rückerl, AA Humbles… - Nature …, 2014 - nature.com
TE Sutherland, N Logan, D Rückerl, AA Humbles, SM Allan, V Papayannopoulos
Nature immunology, 2014nature.com
Enzymatically inactive chitinase-like proteins (CLPs) such as BRP-39, Ym1 and Ym2 are
established markers of immune activation and pathology, yet their functions are essentially
unknown. We found that Ym1 and Ym2 induced the accumulation of neutrophils through the
expansion of γδ T cell populations that produced interleukin 17 (IL-17). While BRP-39 did
not influence neutrophilia, it was required for IL-17 production in γδ T cells, which suggested
that regulation of IL-17 is an inherent feature of mouse CLPs. Analysis of a nematode …
Abstract
Enzymatically inactive chitinase-like proteins (CLPs) such as BRP-39, Ym1 and Ym2 are established markers of immune activation and pathology, yet their functions are essentially unknown. We found that Ym1 and Ym2 induced the accumulation of neutrophils through the expansion of γδ T cell populations that produced interleukin 17 (IL-17). While BRP-39 did not influence neutrophilia, it was required for IL-17 production in γδ T cells, which suggested that regulation of IL-17 is an inherent feature of mouse CLPs. Analysis of a nematode infection model, in which the parasite migrates through the lungs, revealed that the IL-17 and neutrophilic inflammation induced by Ym1 limited parasite survival but at the cost of enhanced lung injury. Our studies describe effector functions of CLPs consistent with innate host defense traits of the chitinase family.
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