A possible role for neutrophils in allergic rhinitis revealed after cellular subclassification

Abstract

A re-examination of former concepts is required to meet today’s medical challenges in allergic rhinitis. Previously, neutrophils have been treated as a relatively homogenous cell population found in the nose both when the patient is suffering at the height of the allergic season as well as when the patient report no symptoms. However, new data indicates that neutrophils can be divided into different subsets with diverse roles in inflammation. We showed increased levels of neutrophils in peripheral blood, nasal biopsies and nasal lavage fluid (NAL) from allergic patients during the pollen season compared to healthy controls. A closer examination revealed that the activated subset of neutrophils, CD16high CD62Ldim, outweighed the normal form CD16high CD62Lhigh in nasal tissue among these patients. This skewed distribution was not seen in controls. The normal subset prevailed in peripheral blood from patients as well as controls, whereas CD16high CD62Ldim and CD16dim CD62Ldim subsets, the latter considered “end state” neutrophils before apoptosis, were elevated in NAL. Functional in vitro experiments revealed that activated neutrophils exhibit a T cell priming capacity and an ability to enhance eosinophil migration. Activated neutrophils may thus contribute to allergic inflammation seen in allergic rhinitis by priming T cells and attracting eosinophils.

Neutrophil Diversity in Health and Disease

“…Notably, similar populations of CD62L low CD16 high neutrophils have been reported in the peripheral blood, nasal biopsies, and nasal lavage fluid of allergic patients [74], as well as in the peripheral blood and bronchoalveolar lavage fluid of infants with different types of viral respiratory infections (e.g., respiratory syncytial virus, bocaviruses, coronavirus, or rhinoviruses) with and without bacterial coinfection (e.g., Haemophilus influenza, Staphylococcus aureus, Streptococcus pneumonia, or Pseudomonas aeruginosa) [75]. However, in the former case (allergy), CD62L low CD16 high neutrophils displayed T cell priming activityrevealed by their ability to increase the expression of CD69 + on naïve CD4 + T cells [74]. In the latter case (viral infections), CD62L low CD16 high neutrophils were defined as immunosuppressive without verifying their ability to inhibit T cell functions in vitro [75].…”

“…These cells were found to inhibit proliferation and cytokine [e.g., IFN-γ and interleukin (IL)-13] production by CD4 + and CD8 + T cell in vitro via CD11b-dependent ROS release [8,73]. Notably, similar populations of CD62L low CD16 high neutrophils have been reported in the peripheral blood, nasal biopsies, and nasal lavage fluid of allergic patients [74], as well as in the peripheral blood and bronchoalveolar lavage fluid of infants with different types of viral respiratory infections (e.g., respiratory syncytial virus, bocaviruses, coronavirus, or rhinoviruses) with and without bacterial coinfection (e.g., Haemophilus influenza, Staphylococcus aureus, Streptococcus pneumonia, or Pseudomonas aeruginosa) [75]. However, in the former case (allergy), CD62L low CD16 high neutrophils displayed T cell priming activityrevealed by their ability to increase the expression of CD69 + on naïve CD4 + T cells [74].…”

The impact of allergen exposure and specific immunotherapy on circulating blood cells in allergic rhinitis

“…IL-17 from Th17 cells was also associated with neutrophil recruitment in AR, probably by inducing IL-8 and CXCL1Groα release by airway fibroblasts. Neutrophils express multiple mediators which mediate airway inflammation such as MMP-9, neutrophil elastase, α-defensin, TGF-ß1 and ROS, supporting eosinophil migration and priming of T cells [ 87 ]. The prolonged release of neutrophil elastase and free radicals damage the epithelium and are most likely responsible for vasomotor symptoms characterizing AR.…”

Dividing neutrophils in subsets reveals a significant role for activated neutrophils in the development of airway hyperreactivity

“…The CD16 high CD62L high ‐expressing neutrophils are mature, but non‐activated, whereas the CD16 high CD62L dim ‐expressing neutrophils are considered to be mature and activated, playing an important role in inflammatory diseases such as systemic inflammation . Subsets of neutrophils with similar antigen presentation characteristics have been produced in vitro using LPS and we have shown that these subsets have specific roles in allergic rhinitis and head and neck squamous cells cancer …”