1. The role of microfibrillar-associated protein 4 (MFAP4) in asthma Bartosz Pilecki PhD student Institute of Molecular Medicine University of Southern Denmark, Odense

2. Asthma Common chronic airway disease Decrease in lung function due to persistent inflammation, airway remodeling and airway hyperresponsiveness (AHR) Current treatments effective only in selected subsets of patients

3. MFAP4 Extracellular matrix (ECM) protein that binds to elastin and collagen Abundant in heart, lung, skin etc. Promotes proliferation and migration of vascular SMC in an integrin-dependent manner (Schlosser et al, submitted) Wulf-Johansson et al, 2013

4. Hypothesis: MFAP4 contributes to asthmatic airway disease, mainly due to its interaction with airway smooth muscle cells

5. In vivo allergy models OVA model:House dust mite (HDM) chronic model: Day: 0-4 5-6 rest 25 ug HDM i.n. 7 weeks

6. MFAP4 levels are increased in asthma WT OVA WT PBS

7. MFAP4 deficiency attenuates eosinophilic infiltration

8. Eosinophil chemoattractants are downregulated in MFAP4-deficient mice

9. Lack of MFAP4 attenuates mucus production PBS KO OVA WT OVA

10. MFAP4 contributes to asthmatic smooth muscle deposition

11. MFAP4 deficiency partially protects from AHR

12. Conclusions MFAP4 is increased in circulation and BAL of asthmatic mice. MFAP4 contributes to development of experimental asthma by: 1.Attraction of eosinophils through CCL11/CCL24 2.Goblet cell metaplasia 3.Smooth muscle deposition 4.AHR It suggests that MFAP4 can be a potential therapeutic target for allergic asthma.

13. Acknowledgements Christopher Stevenson, Novartis, UK Jorgen Vestbo, OUH, DK Niels Marcussen, OUH, DK Fonden til laegevidenskabens fremme