Expression of TSLP and IL-33 receptors on sputum macrophages of asthma patients and healthy subjects

J Asthma. 2020 Jan;57(1):1-10. doi: 10.1080/02770903.2018.1543435. Epub 2018 Dec 27.

Abstract

Objective: Local cytokine milieu (especially Th2 inflammatory type) secreted into the asthmatic airways affect the alternative activated macrophages polarization (M2). TSLP and IL-33 are important alarmins of allergic response associated with Th2 inflammation. The aim of the study was to investigate the expression of the receptors for epithelial derived cytokines: TSLP (TSLPR) and IL-33 (ST2) on induced sputum CD206 positive macrophages from asthma and healthy subjects and analyze the relationships between these receptors and clinical features of the disease. Methods: Immunofluorescence staining for CD206 and TSLPR or ST2 on sputum macrophages was performed in 20 adult patients with stable asthma - 75% with atopy (3 intermittent, 12 mild-to-moderate, 5 severe, of which 11 were on biological anty-IgE treatment) and 23 healthy adult controls - 48% with atopy. Results: Our study demonstrated an increased expression of TSLP and IL-33 receptors on bronchial CD206 positive macrophages in asthma group. TSLPR but not ST2 had also greater expression on CD206 negative macrophages in asthma patients. Increased expression of both investigated receptors was related to longer disease duration and impaired lung function. We observed increased count of CD206lowTSLPhigh macrophages as well as positive correlation of these cells with total serum IgE in patients with atopy. Conclusions: The macrophage response during allergic reaction is likely to be connected with TSLP but rather not with IL-33 action. Our study indicates an important role of crosstalk between macrophages, TSLP and IL-33 in asthma pathophysiology.

Keywords: IL-33; TSLP; asthma; macrophages.

MeSH terms

  • Adult
  • Asthma / immunology*
  • Asthma / pathology
  • Cross-Sectional Studies
  • Cytokines / immunology
  • Cytokines / metabolism
  • Female
  • Healthy Volunteers
  • Humans
  • Interleukin-1 Receptor-Like 1 Protein / immunology
  • Interleukin-1 Receptor-Like 1 Protein / metabolism*
  • Interleukin-33 / immunology
  • Interleukin-33 / metabolism
  • Lectins, C-Type / metabolism
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Male
  • Mannose Receptor
  • Mannose-Binding Lectins / metabolism
  • Middle Aged
  • Prospective Studies
  • Receptors, Cell Surface / metabolism
  • Receptors, Cytokine / immunology
  • Receptors, Cytokine / metabolism*
  • Sputum / cytology
  • Sputum / immunology

Substances

  • CRLF2 protein, human
  • Cytokines
  • IL1RL1 protein, human
  • IL33 protein, human
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Lectins, C-Type
  • Mannose Receptor
  • Mannose-Binding Lectins
  • Receptors, Cell Surface
  • Receptors, Cytokine
  • TSLP protein, human