House Dust Mite Induces Bone Marrow IL-33-Responsive ILC2s and TH Cells

Int J Mol Sci. 2020 May 26;21(11):3751. doi: 10.3390/ijms21113751.

Abstract

Type 2 innate lymphoid cells (ILC2s) and their adaptive counterpart type 2 T helper (TH2) cells respond to interleukin-33 (IL-33) by producing IL-5, which is a crucial cytokine for eosinophil development in the bone marrow. The aim of this study was to determine if bone marrow ILC2s, TH cells, and eosinophils are locally regulated by IL-33 in terms of number and activation upon exposure to the common aeroallergen house dust mite (HDM). Mice that were sensitized and challenged with HDM by intranasal exposures induced eosinophil development in the bone marrow with an initial increase of IL5Rα+ eosinophil progenitors, following elevated numbers of mature eosinophils and the induction of airway eosinophilia. Bone marrow ILC2s, TH2, and eosinophils all responded to HDM challenge by increased IL-33 receptor (ST2) expression. However, only ILC2s, but not TH cells, revealed increased ST2 expression at the onset of eosinophil development, which significantly correlated with the number of eosinophil progenitors. In summary, our findings suggest that airway allergen challenges with HDM activates IL-33-responsive ILC2s, TH cells, and eosinophils locally in the bone marrow. Targeting the IL-33/ST2 axis in allergic diseases including asthma may be beneficial by decreasing eosinophil production in the bone marrow.

Keywords: IL-33; IL-5; ST2; T helper cells; adaptive immunity; allergy; asthma; eosinophilia; innate lymphoid cells; type 2 inflammation.

MeSH terms

  • Animals
  • Antigens, Dermatophagoides / immunology*
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / immunology*
  • Cell Differentiation
  • Cells, Cultured
  • Eosinophils / cytology
  • Eosinophils / immunology*
  • Interleukin-33 / immunology*
  • Interleukin-5 Receptor alpha Subunit / genetics
  • Interleukin-5 Receptor alpha Subunit / metabolism
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Th2 Cells / cytology
  • Th2 Cells / immunology*

Substances

  • Antigens, Dermatophagoides
  • Interleukin-33
  • Interleukin-5 Receptor alpha Subunit