Interactions between eosinophils and IL-5Rα-positive mast cells in nonadvanced systemic mastocytosis

Guillaume Lefèvre; Jean-Baptiste Gibier; Antonino Bongiovanni; Ludovic Lhermitte; Julien Rossignol; Emilie Anglo; Arnaud Dendooven; Romain Dubois; Louis Terriou; David Launay; Stéphane Barete; Stéphane Esnault; Laurent Frenzel; Clément Gourguechon; Thomas Ballul; Frédéric Dezoteux; Delphine Staumont-Salle; Marie-Christine Copin; Rachel Rignault-Bricard; Thiago Trovati Maciel; Gandhi Damaj; Meryem Tardivel; Marie Crinquette-Verhasselt; Patrice Dubreuil; Leila Maouche-Chrétien; Julie Bruneau; Olivier Lortholary; Nicolas Duployez; Hélène Behal; Thierry Jo Molina; Olivier Hermine

doi:10.1016/j.jaci.2024.07.025

Interactions between eosinophils and IL-5Rα-positive mast cells in nonadvanced systemic mastocytosis

J Allergy Clin Immunol. 2024 Dec;154(6):1523-1533. doi: 10.1016/j.jaci.2024.07.025. Epub 2024 Aug 14.

Authors

Guillaume Lefèvre¹, Jean-Baptiste Gibier², Antonino Bongiovanni³, Ludovic Lhermitte⁴, Julien Rossignol⁵, Emilie Anglo⁶, Arnaud Dendooven⁶, Romain Dubois², Louis Terriou⁷, David Launay⁷, Stéphane Barete⁸, Stéphane Esnault⁹, Laurent Frenzel⁵, Clément Gourguechon¹⁰, Thomas Ballul⁵, Frédéric Dezoteux¹¹, Delphine Staumont-Salle¹¹, Marie-Christine Copin¹², Rachel Rignault-Bricard¹³, Thiago Trovati Maciel¹³, Gandhi Damaj¹⁴, Meryem Tardivel³, Marie Crinquette-Verhasselt², Patrice Dubreuil¹⁵, Leila Maouche-Chrétien¹³, Julie Bruneau¹⁶, Olivier Lortholary¹⁷, Nicolas Duployez¹⁸, Hélène Behal¹⁹, Thierry Jo Molina²⁰, Olivier Hermine²¹

Affiliations

¹ University of Lille, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire (CHU) Lille, and Institute for Translational Research in Inflammation (INFINITE), Lille, France; Institut d'Immunologie, CHU Lille, Lille, France; National Reference Center for Hypereosinophilic Syndromes (CEREO). Electronic address: [email protected].
² University of Lille, Institut de Pathologie, Centre de Biopathologie, CHU Lille, Lille, France.
³ Centre National de la Recherche Scientifique (CNRS), INSERM, CHU Lille, University of Lille, Institut Pasteur de Lille, Lille, France.
⁴ Laboratoire d'Onco-Hématologie, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France; University of Paris, Institut Imagine, INSERM, Paris, France; French Reference Center for Mastocytosis (CEREMAST), Hôpital Necker-Enfants Malades, AP-HP, Paris, France.
⁵ University of Paris, Institut Imagine, INSERM, Paris, France; French Reference Center for Mastocytosis (CEREMAST), Hôpital Necker-Enfants Malades, AP-HP, Paris, France; Department of Hematology, Hôpital Necker-Enfants Malades, AP-HP, Paris, France.
⁶ University of Lille, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire (CHU) Lille, and Institute for Translational Research in Inflammation (INFINITE), Lille, France; Institut d'Immunologie, CHU Lille, Lille, France.
⁷ University of Lille, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire (CHU) Lille, and Institute for Translational Research in Inflammation (INFINITE), Lille, France; National Reference Center for Hypereosinophilic Syndromes (CEREO); Département de Médecine Interne et Immunologie Clinique, CHU Lille, Lille, France.
⁸ CEREMAST, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Unit de Dermatologie, Sorbonne Université Paris, Paris, France.
⁹ University of Lille, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire (CHU) Lille, and Institute for Translational Research in Inflammation (INFINITE), Lille, France; Institut d'Immunologie, CHU Lille, Lille, France; Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wis.
¹⁰ Department of Hematology, CHU Amiens, Amiens, France.
¹¹ University of Lille, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire (CHU) Lille, and Institute for Translational Research in Inflammation (INFINITE), Lille, France; National Reference Center for Hypereosinophilic Syndromes (CEREO); Department of Dermatology, CHU Lille, Lille, France.
¹² Department of Pathology, CHU Angers, University of Angers, INSERM, CNRS, CRCI(2)NA, Angers, France.
¹³ University of Paris, Institut Imagine, INSERM, Paris, France.
¹⁴ Institut d'Hématologie, University of Caen Normandie, Caen, France.
¹⁵ Signaling, Hematopoiesis, and Mechanism of Oncogenesis (CRCM), CEREMAST, and Association Française pour les Initiatives de Recherche sur le Mastocyte et les Mastocytose (AFIRMM) studies, INSERM U1068; Institut Paoli-Calmettes; UM105, Aix-Marseille University; and CNRS, UMR7258, Marseille, France.
¹⁶ University of Paris, Institut Imagine, INSERM, Paris, France; French Reference Center for Mastocytosis (CEREMAST), Hôpital Necker-Enfants Malades, AP-HP, Paris, France; Department of Pathology, Hôpital Necker-Enfants Malades, AP-HP, Paris, France.
¹⁷ University of Paris, Institut Imagine, INSERM, Paris, France; French Reference Center for Mastocytosis (CEREMAST), Hôpital Necker-Enfants Malades, AP-HP, Paris, France.
¹⁸ CNRS, INSERM, CHU Lille, Cancer Heterogeneity, Plasticity, and Resistance to Therapies (CANTHER), University of Lille, Institut d'Hématologie, CHU Lille, Lille, France.
¹⁹ University of Lille, CHU Lille, Evaluation des Technologies de Santé et des Pratiques Médicales (METRICS), Lille, France.
²⁰ University of Paris, Institut Imagine, INSERM, Paris, France; Signaling, Hematopoiesis, and Mechanism of Oncogenesis (CRCM), CEREMAST, and Association Française pour les Initiatives de Recherche sur le Mastocyte et les Mastocytose (AFIRMM) studies, INSERM U1068; Institut Paoli-Calmettes; UM105, Aix-Marseille University; and CNRS, UMR7258, Marseille, France.
²¹ University of Paris, Institut Imagine, INSERM, Paris, France; French Reference Center for Mastocytosis (CEREMAST), Hôpital Necker-Enfants Malades, AP-HP, Paris, France; Department of Hematology, Hôpital Necker-Enfants Malades, AP-HP, Paris, France. Electronic address: [email protected].

PMID: 39151478
DOI: 10.1016/j.jaci.2024.07.025

Abstract

Background: Bidirectional interactions between eosinophils and mast cells (MCs) have been reported in various allergic diseases. Bone marrow (BM) eosinophilia, and to a lesser extent blood eosinophilia, is common in systemic mastocytosis (SM), but its significance remains unknown.

Objective: We described blood and BM eosinophil characteristics in SM.

Methods: A large collection of BM biopsy samples was analyzed using immunohistochemical staining and whole-slide imaging. Eosinophil and extracellular granules were detected by eosinophil peroxidase (EPX) staining and MCs by KIT staining. Complementary analyses were conducted using flow cytometry and immunofluorescence.

Results: Eosinophil infiltrates and large areas of eosinophil degranulation were observed within or around BM MC infiltrates in SM. EPX staining surface, highlighting intact eosinophils and eosinophil degranulation, was higher in nonadvanced SM (n = 37 BM biopsy samples) compared with both controls (n = 8, P = .0003) and advanced SM (n = 24, P = .014). In nonadvanced SM, positive correlations were observed between serum tryptase levels and percentages of eosinophil counts in BM aspirations (Spearman r coefficient r = 0.38, P = .038), eosinophils count in BM biopsy samples (r = 0.45, P = .007), EPX staining (r = 0.37, P = .035), and eosinophil degranulation (r = 0.39, P = .023). Eosinophil counts in BM biopsy samples also correlated with MC counts (r = 0.47, P = .006) and KIT staining surface (r = 0.49, P = .003). BM MCs expressed IL-5 receptor and other usual eosinophil cytokine/chemokine receptors, and blood eosinophils displayed several increased surface markers compared with controls, suggesting an activated state.

Conclusion: Our data suggest possible cross talk between MCs and eosinophils, supporting MC tryptase release and MC activation-related symptoms. This suggests a rationale for targeting eosinophils in nonadvanced SM not fully controlled by other therapies.

Keywords: Eosinophil; mast cell; systemic mastocytosis.

MeSH terms

Adult
Aged
Bone Marrow / immunology
Bone Marrow / metabolism
Bone Marrow / pathology
Cell Communication / immunology
Cell Degranulation
Eosinophil Peroxidase / metabolism
Eosinophils* / immunology
Eosinophils* / pathology
Female
Humans
Interleukin-5 Receptor alpha Subunit* / immunology
Interleukin-5 Receptor alpha Subunit* / metabolism
Male
Mast Cells* / immunology
Mast Cells* / metabolism
Mast Cells* / pathology
Mastocytosis, Systemic* / diagnosis
Mastocytosis, Systemic* / immunology
Mastocytosis, Systemic* / metabolism
Mastocytosis, Systemic* / pathology
Middle Aged
Tryptases / blood
Tryptases / metabolism

Substances

Interleukin-5 Receptor alpha Subunit
Tryptases
IL5RA protein, human
Eosinophil Peroxidase