Charcot–Leyden crystals and other protein crystals driving type 2 immunity and allergy

Abstract

Protein crystals derived from innate immune cells have been synonymous with a Type-2 immune response in both mouse and man for over 150 years. Eosinophilic Galectin-10 (Charcot-Leyden) crystals in humans, and Ym1/Ym2 crystals in mice are frequently found in the context of parasitic infections, but also in diseases such as asthma and chronic rhinosinusitis. Despite their notable presence, these crystals are often overlooked as trivial markers of Type-2 inflammation. Here, we discuss the source, context, and role of protein crystallization. We focus on similarities observed between Galectin-10 and Ym1/2 crystals in driving immune responses; the subsequent benefit to the host during worm infection, and conversely the detrimental exacerbation of inflammation and mucus production during asthma.

Advances in chronic rhinosinusitis in 2020 and 2021

“…7 Recent studies have underlined the important role for CLCs in the pathophysiology of CRS. 63 CLCs are the crystalized form of galectin-10 protein, released during EETosis, and are therefore abundantly present in both the mucus and the near-denuded epithelium in the mucosa of both patients with CRSsNP and patients with CRSwNP. 18 In their close proximity with epithelial cells, CLCs are able to sustain a neutrophilic migration both in vitro and in mouse models, and thus sustaining a chronic mixed eosinophilic-neutrophilic inflammation.…”

Advancing Lung Immunology Research: An Official American Thoracic Society Workshop Report

“…CLC treatment also promoted antigen-specific T cell responses and increased antigen-specific antibody responses in vivo ( 238 ). Of note, type 2 immunity in mice also triggers protein crystal formation, which is due to crystallization of two closely related chitinase-like proteins, Ym1 (Chil3) and Ym2 (Chil4) ( 239 ). Defining the biology of CLC and pseudo-CLC (Ym1 and Ym2 crystals) and their function in type 2 immunity is an ongoing area of investigation.…”

“…For example, for .100 years, eosinophilic inflammatory diseases such as asthma, chronic rhinosinusitis with nasal polyps, and allergic bronchopulmonary aspergillosis have been associated with extracellular deposits of morphologically diverse crystals. First described by Charcot followed by Leyden in the 19th century, Charcot-Leyden crystals (CLCs) are composed of Gal10 (galectin-10), which is one of the most abundant proteins in human eosinophils (236)(237)(238)(239). However, mice lack an ortholog of Gal10, and, as a result, it had remained unclear whether CLCs regulate disease or represent a bystander phenomenon during eosinophilic inflammation in vivo.…”

La neurotoxine dérivée des éosinophiles (EDN) : intérêt du dosage dans les pathologies mastocytaires

“…Lorsqu'ils sont phagocytés par les macrophages, ils conduisent à la production de la cytokine proinflammatoire IL-1β (46). Ils sont largement présents dans les réponses immunes de type Th2 (47) notamment l'asthme, la polypose naso-sinusienne ou les infections parasitaires (48).…”