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

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.

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Complement factor C5 inhibition reduces type 2 responses without affecting group 2 innate lymphoid cells in a house dust mite induced murine asthma model

Respiratory Research ◽

10.1186/s12931-019-1136-5 ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 3

Author(s):

Jack Yang ◽

Ivan Ramirez Moral ◽

Cornelis van ’t Veer ◽

Alex F. de Vos ◽

Regina de Beer ◽

...

Keyword(s):

House Dust ◽

House Dust Mite ◽

Innate Lymphoid Cells ◽

Lymphoid Cells ◽

Complement Factor ◽

Asthma Model ◽

Dust Mite ◽

Group 2 ◽

Murine Asthma Model

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Metabolic Interdependency of Th2 Cell-Mediated Type 2 Immunity and the Tumor Microenvironment

Frontiers in Immunology ◽

10.3389/fimmu.2021.632581 ◽

2021 ◽

Vol 12 ◽

Author(s):

Simon Schreiber ◽

Christoph M. Hammers ◽

Achim J. Kaasch ◽

Burkhart Schraven ◽

Anne Dudeck ◽

...

Keyword(s):

T Cells ◽

Tumor Microenvironment ◽

Allergic Diseases ◽

Building Blocks ◽

Th2 Cells ◽

Th Cells ◽

Th2 Cell ◽

Type 2 Immunity ◽

Mediate Immunity

The function of T cells is critically dependent on their ability to generate metabolic building blocks to fulfil energy demands for proliferation and consecutive differentiation into various T helper (Th) cells. Th cells then have to adapt their metabolism to specific microenvironments within different organs during physiological and pathological immune responses. In this context, Th2 cells mediate immunity to parasites and are involved in the pathogenesis of allergic diseases including asthma, while CD8+ T cells and Th1 cells mediate immunity to viruses and tumors. Importantly, recent studies have investigated the metabolism of Th2 cells in more detail, while others have studied the influence of Th2 cell-mediated type 2 immunity on the tumor microenvironment (TME) and on tumor progression. We here review recent findings on the metabolism of Th2 cells and discuss how Th2 cells contribute to antitumor immunity. Combining the evidence from both types of studies, we provide here for the first time a perspective on how the energy metabolism of Th2 cells and the TME interact. Finally, we elaborate how a more detailed understanding of the unique metabolic interdependency between Th2 cells and the TME could reveal novel avenues for the development of immunotherapies in treating cancer.

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PI3Kδ Inhibition Prevents IL33, ILC2s and Inflammatory Eosinophils in Persistent Airway Inflammation

10.21203/rs.3.rs-209463/v1 ◽

2021 ◽

Author(s):

Sorif Uddin ◽

Augustin Amour ◽

David J Lewis ◽

Chris D Edwards ◽

Matthew G Williamson ◽

...

Keyword(s):

Airway Inflammation ◽

Goblet Cell ◽

House Dust ◽

House Dust Mite ◽

Inflammatory Responses ◽

Lymphoid Cells ◽

Antibody Treatment ◽

Dust Mite ◽

Group 2 ◽

Goblet Cell Metaplasia

Abstract Background: Phosphoinositide-3-kinase-delta (PI3Kδ) inhibition is a promising therapeutic approach for inflammatory conditions due to its role in leucocyte proliferation, migration and activation. However, the effect of PI3Kδ inhibition on group-2-innate lymphoid cells (ILC2s) and inflammatory eosinophils remains unknown. Using a murine model exhibiting persistent airway inflammation we sought to understand the effect of PI3Kδ inhibition, montelukast and anti-IL5 antibody treatment on IL33 expression, group-2-innate lymphoid cells, inflammatory eosinophils, and goblet cell metaplasia. Results: Mice were sensitised to house dust mite and after allowing inflammation to resolve, were re-challenged with house dust mite to re-initiate airway inflammation. ILC2s were found to persist in the airways following house dust mite sensitisation and after re-challenge their numbers increased further along with accumulation of inflammatory eosinophils. In contrast to montelukast or anti-IL5 antibody treatment, PI3Kδ inhibition ablated IL33 expression and prevented group-2-innate lymphoid cell accumulation. Only PI3Kδ inhibition and IL5 neutralization reduced the infiltration of inflammatory eosinophils. Moreover, PI3Kδ inhibition reduced goblet cell metaplasia. Conclusions: Hence, we show that PI3Kδ inhibition dampens allergic inflammatory responses by ablating key cell types and cytokines involved in T-helper-2-driven inflammatory responses.

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