Ym1 protein crystals promote type 2 immunity
Ines Heyndrickx1,2, Kim Deswarte1,2, Kenneth Verstraete3,4
1Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium.
Murine pseudo-Crystalloids of Charcot-Leyden (CLCs), made of Ym1/Ym2 proteins, stimulate innate and adaptive immunity. These protein crystals act as a type 2 immune adjuvant, reinforcing eosinophilic inflammation.
Area of Science:
- Immunology
- Crystallography
- Protein Science
Background:
- Spontaneous protein crystallization is rare but observed in eosinophil-rich inflammation.
- Human Charcot-Leyden crystals (CLCs) are composed of galectin-10 (Gal10).
- Mice form pseudo-CLCs from chitinase-like proteins Ym1 and Ym2.
Purpose of the Study:
- To investigate the biological effects of pseudo-CLCs.
- To understand the function of Ym1 and Ym2 protein crystals in vivo.
- To explore their role in eosinophilic inflammation.
Main Methods:
- Production of recombinant Ym1 protein crystals.
- X-ray crystallography to determine crystal structure and packing.
- Administration of crystalline and soluble Ym1 to murine airways.
- Assessment of innate and adaptive immune responses, including dendritic cell (DC) activation.
Main Results:
- Recombinant Ym1 crystals exhibit identical structure and packing to native murine crystals.
- Crystalline Ym1, but not soluble Ym1, stimulates innate and adaptive immunity.
- Ym1 crystals act as a type 2 immune adjuvant, promoting eosinophilic inflammation.
- Dendritic cells (DCs) are triggered by Ym1 crystals.
Conclusions:
- Murine Ym1 protein crystals reinforce type 2 immunity at sites of eosinophilic inflammation.
- Pseudo-CLCs can serve as a valuable model for studying human CLC biology.
- Ym1 crystals modulate immune responses, highlighting their biological significance.
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