Rationale
IL-33 and its receptor IL-1RL1 are important asthma genes. T helper-2 (TH2) cells present in asthmatic airway wall contribute to chronic inflammation and epithelial remodeling. TH2 cells express IL-1RL1 and respond to IL-33 by increased cytokine production upon stimulation. We aimed to test the extent of the IL-33-driven modification of Th2 cell activation, and whether the asthma-susceptibility alleles of IL1RL affect this response. 
Methods
CD4+ T cells isolated from PBMCs of 16 healthy donors and 16 asthma patients, stratified for IL-1RL1 high and low risk-genotypes, were differentiated into TH2 cells in vitro, and re-stimulated by CD3/CD28-crosslinking in presence or absence of 100 ng/mL rhIL-33. Gene expression was assessed by RNA-sequencing, and subsequently analyzed using limma in R comparing high and low risk genotype and asthma versus controls. Membrane bound IL1-RL1-b protein levels were determined using FACS.
Results
Presence of IL-33 during CD3/CD28 stimulation of TH2 effector cells in vitro results in extensive changes in gene expression, affecting up to 40% of the transcriptomic changes induced by TH2 cell activation. The fold change in gene expression induced by IL-33 was significantly higher in TH2 cells carrying the IL-1RL1 risk haplotype compared to the IL-1RL protective haplotype. However, the identity of the IL-33 regulated genes was not different between the IL-1RL1 haplotype groups. In addition, significant differences in IL-33 regulated genes were observed between Th2 cells derived from healthy controls and asthma patients. At the protein level, the change in TH2 cells expressing the transmembrane IL-1RL1 receptor was higher in asthma patients than in controls . 
Conclusions
The asthma-associated IL-1RL1 haplotype strongly increases the sensitivity of TH2 effector cell for IL-33-mediated regulation of gene expression, while disease status also has an independent effect. IL-33 in the airway wall will contribute to chronic inflammation maintained by TH2 effector cells mainly in patients with asthma carrying the IL-1RL1 asthma risk alleles. 


Enhanced IL-33 response in differentiated human TH2 cells carrying the IL-1RL1 asthma risk genotype

poster

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### **Welcome Message**

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The Dutch Lung Congress aims to bring together everyone interested in research related to pulmonary diseases in the Netherlands.  We hope this event will provide opportunities for multidisciplinary interactions to enhance our approaches for addressing these challenging diseases.  Each session will include input from patients, clinical and basic and/or translational scientists discussing the latest information around the central themes chosen by the organizing committee.  One advantage of holding our congress as a virtual event this year is that we will have the opportunity to hear from world leading experts from all over the globe.  We hope you enjoy the programme the organizing committee have put together and will engage in dynamic discussions with all the speakers.

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<br>**Janette Burgess
<br>Chair, DLC Organizing Committee**
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### Special Session: Publieksmiddag
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**More about the committee team:**:
[Barbro N. Melgert, PhD] (https://drive.google.com/file/d/1q_IIH3JvTivumCUzzsZGX7BgD41HxQmk/view?usp=sharing)
// [Bas Holverda, PhD] (https://drive.google.com/file/d/1QKXHmTTQjgs4OZVuM8doXU055S-fu_uU/view?usp=sharing)
// [Frits Franssen, PhD] (https://drive.google.com/file/d/1d7HRUJaqGuRFzkPN3SVgkbBfqFkDkWq2/view?usp=sharing)
// [Janette Burgess, PhD] (https://drive.google.com/file/d/1VHFlrEN6uCQGeeW3Lj4I8aTw7HsB0GFr/view?usp=sharing)
// [Michel van den Heuvel, PhD] (https://drive.google.com/file/d/1JeOEP8MHxiK_4lONr8UM2HaxdxpkAmA2/view?usp=sharing)
// [Patrick Bhairosing] (https://drive.google.com/file/d/1xI8ORq-g1bbVcrlRDviZ9NhAwanc4dFl/view?usp=sharing)
// [Gimano Amatngalim, PhD] (https://drive.google.com/file/d/1fyVDDKARLNjRk_JZk8_GyhGMjmp6DWHp/view?usp=sharing)
// [Peter Kunst, PhD] (https://drive.google.com/file/d/1QhtB4nQezpAjbfUAcBnINc-Bm3Shy2Lf/view?usp=sharing)
// [Dr. Michel van den Heuvel, Prof., MD, PhD] (https://drive.google.com/file/d/1JBdNEBXZCEikEZhJ6MoD5DhQfXMz3bP6/view?usp=sharing)
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Enhanced IL-33 response in differentiated human TH2 cells carrying the IL-1RL1 asthma risk genotype

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