Granulocyte-colony stimulating factor: Missing link for stratification of type 2–high and type 2–low chronic rhinosinusitis patients

• Published in: Journal of allergy and clinical immunology Vol. 149; no. 5; pp. 1655 - 1665.e5
• Main Authors: Van Nevel, Sharon, Declercq, Jozefien, Holtappels, Gabriele, Lambrecht, Bart N., Bachert, Claus
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2022
• Subjects: chronic rhinosinusitis; Granulocyte-colony stimulating factor; Medicin och hälsovetenskap; neutrophils; omalizumab; type 2–low inflammation; CXCL; G-CSFR; IL-1ra; CRS; IHC; CRSwNP; G-CSF; MPO; CRSsNP; ECP; CXCR2; ROS; chronic rhinosinusitis; type 2–low inflammation; Granulocyte-colony stimulating factor; omalizumab; NET; neutrophils
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2022.02.019

Chronic rhinosinusitis (CRS) is a heterogeneous disease, with patients having either a high or low type 2 inflammatory endotype. Whereas the type 2–high group is well characterized by IL-5 expression, the type 2–low group, consisting of approximately 20% of CRS with and 50% of CRS without nasal polyp patients, lacks a clear biomarker profile and thus specific therapeutic targets. The aim was to identify underlying molecular pathways of type 2–low CRS, as stratification of patients may allow improvement of personalized treatments. Luminex assays were performed to analyze proteins in nasal secretions and tissues of CRS patients. Immunostainings were analyzed for differences in neutrophils, granulocyte-colony stimulating factor (G-CSF), and its receptor in nasal tissue. Neutrophils were isolated from blood of healthy volunteers and stimulated with G-CSF. Effects on apoptosis and neutrophil activity were analyzed with flow cytometry. G-CSF was significantly upregulated in nasal tissue and secretion fluid of type 2–low CRS patients compared to type 2–high patients. In nasal polyp tissue of type 2–low patients, a large infiltration of neutrophils expressing both G-CSF and its receptor was detected, suggesting the presence of a neutrophil-intrinsic autocrine survival mechanism. In response to G-CSF, neutrophils were in an activated state and were resistant to apoptosis, possibly contributing to a chronic inflammation. Of interest, type 2–high nasal polyp patients treated with IgE-blocking omalizumab had increased G-CSF concentrations compared to before treatment. G-CSF is an important cytokine regulating neutrophils in type 2–low CRS and has potential in the diagnosis and therapy of the disease.