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

Emma Boberg,Julie Weidner,Kristina Johansson,Madeleine Rådinger,Carina Malmhäll

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.

Highlights

Type 2 innate lymphoid cells (ILC2s) are effector cells typically located at mucosal surfaces where they respond rapidly to environmental insults such as allergens in an antigen-independent manner [1,2,3]
We have previously shown that a higher number of mature eosinophils express ST2 in a direct IL-33-induced asthma model compared to control mice [22] and we recently observed a higher number of ST2+ eosinophils and IL-33-responsive ILC2s in the bone marrow in an IL-33- dependent acute protease allergen model [33]
These data suggest that airway exposure to house dust mite (HDM) promotes eosinophil hematopoiesis in the bone marrow, where an early induction of eosinophil progenitors is followed by eosinophil maturation

Summary

Introduction

Type 2 innate lymphoid cells (ILC2s) are effector cells typically located at mucosal surfaces where they respond rapidly to environmental insults such as allergens in an antigen-independent manner [1,2,3]. Airway allergen challenge triggers the release of epithelial-derived interleukin (IL)-33, which activates cells that express the IL-33 receptor (ST2) such as ILC2s and CD4+ T helper (TH) cells, including type 2 T helper cells (TH2) and regulatory T cells [15,16,17,18]. ST2 is strongly associated with the function of TH2 cells [19], it has been shown that TH1 cells can transiently express ST2 upon differentiation during viral infection [20]. Cytokine production by T cells is one of the key characteristics of IL-33 [21] Both TH2 cells and ILC2s produce type 2 cytokines such as IL-4, IL-5, and IL-13 upon activation at sites of inflammation [14]. We have previously shown in an IL-33-induced mouse model of type 2 airway inflammation that bone marrow ILC2s locally produce

Objectives

Methods

Results