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Role of protein crystallization in type 2 immunity and asthma

Objective

Spontaneous protein crystallization is a rare event in biology. Eosinophilic inflammation such as seen in the airways in asthma, chronic rhinosinusitis and helminth infection is however accompanied by accumulation of large amounts of extracellular Charcot-Leyden crystals. These are made of Galectin-10, a protein of unknown function produced by eosinophils, hallmark cells of type 2 immunity. In mice, eosinophilic inflammation is also accompanied by protein crystal build up, composed of the chitinase-like proteins Ym1 and Ym2, produced by alternatively activated macrophages. Here we challenge the current view that these crystals are just markers of eosinophil demise or macrophages activation. We hypothesize that protein crystallization serves an active role in immunoregulation of type 2 immunity. On the one hand, crystallization might turn a harmless protein into a danger signal. On the other hand, crystallization might sequester and eliminate the physiological function of soluble Galectin-10 and Ym1, or prolong it via slow release elution. For full understanding, we therefore need to understand the function of the proteins in a soluble and crystalline state. Our program at the frontline of immunology, molecular structural biology and clinical science combines innovative tool creation and integrative research to investigate the structure, function, and physiology of galectin-10 and related protein crystals. We chose to study asthma as the crystallizing proteins are abundantly present in human and murine disease. There is still a large medical need for novel therapies that could benefit patients with chronic steroid-resistant disease, and are alternatives to eosinophil-depleting antibodies whose long term effects are unknown.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

ERC-ADG - Advanced Grant

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Call for proposal

(opens in new window) ERC-2017-ADG

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Host institution

VIB VZW
Net EU contribution
€ 2 499 846,00
Address
SUZANNE TASSIERSTRAAT 1
9052 ZWIJNAARDE - GENT
Belgium
Region
Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent
Activity type
Research Organisations
Links
Total cost
€ 2 499 846,00

Beneficiaries (1)