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

Tara E Sutherland; Nicola Logan; Dominik Rückerl; Alison A Humbles; Stuart M Allan; Venizelos Papayannopoulos; Brigitta Stockinger; Rick M Maizels; Judith E Allen

doi:10.1038/ni.3023

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

Tara E Sutherland, Nicola Logan, Dominik Rückerl, Alison A Humbles, Stuart M Allan, Venizelos Papayannopoulos, Brigitta Stockinger, Rick M Maizels, Judith E Allen

School of Biological Sciences

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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.

Original language	English
Pages (from-to)	1116-1125
Number of pages	10
Journal	Nature Immunology
Volume	15
Issue number	12
DOIs	https://doi.org/10.1038/ni.3023
Publication status	Published - 19 Oct 2014

Access to Document

10.1038/ni.3023

AllenEtalNI2O14Chitinase-likeProteinsPromoteIL-17-mediatedNeutrophiliaAccepted author manuscript, 8.98 MB

The Chitinase Family: does sibling rivalry shape lung homeostasis, inflmmation and response to helminth-induced damage/
Allen, J. & Maizels, R.
MRC
15/03/12 → 14/03/15
Project: Research
Centre for Immunity, Infection and Evolution
Matthews, K.
UK-based charities
1/10/11 → 31/03/17
Project: Research
Weighing up the long-term consequences of chitanase inhibition for asthma and allergy therapy
Allen, J. & Maizels, R.
UK-based charities
15/03/11 → 14/03/12
Project: Research

Judi Allen
- School of Biological Sciences - UoE Honorary staff
Person: Affiliated Independent Researcher

Cite this

@article{0de00141359343fbbdf87f292b404582,

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

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.",

author = "Sutherland, {Tara E} and Nicola Logan and Dominik R{\"u}ckerl and Humbles, {Alison A} and Allan, {Stuart M} and Venizelos Papayannopoulos and Brigitta Stockinger and Maizels, {Rick M} and Allen, {Judith E}",

year = "2014",

month = oct,

day = "19",

doi = "10.1038/ni.3023",

language = "English",

volume = "15",

pages = "1116--1125",

journal = "Nature Immunology",

issn = "1529-2908",

publisher = "Nature Publishing Group",

number = "12",

}

TY - JOUR

T1 - Chitinase-like proteins promote IL-17-mediated neutrophilia in a tradeoff between nematode killing and host damage

AU - Sutherland, Tara E

AU - Logan, Nicola

AU - Rückerl, Dominik

AU - Humbles, Alison A

AU - Allan, Stuart M

AU - Papayannopoulos, Venizelos

AU - Stockinger, Brigitta

AU - Maizels, Rick M

AU - Allen, Judith E

PY - 2014/10/19

Y1 - 2014/10/19

N2 - 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.

AB - 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.

U2 - 10.1038/ni.3023

DO - 10.1038/ni.3023

M3 - Article

C2 - 25326751

SN - 1529-2908

VL - 15

SP - 1116

EP - 1125

JO - Nature Immunology

JF - Nature Immunology

IS - 12

ER -

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

Abstract / Description of output

Access to Document

Fingerprint

Projects

The Chitinase Family: does sibling rivalry shape lung homeostasis, inflmmation and response to helminth-induced damage/

Centre for Immunity, Infection and Evolution

Weighing up the long-term consequences of chitanase inhibition for asthma and allergy therapy

Profiles

Judi Allen

Cite this