Salt-inducible kinase (SIK) inhibition is protective in a mouse model of asthma

Interleukin-13 (IL-13) and other Th2 cytokines are important regulators of airway hyper-responsiveness, immune cell infiltration and inflammation in allergic asthma, and are produced when immune cells, such as type 2 innate lymphoid cells (ILC2s) and mast cells, are stimulated with IL-33. Here, we report that the IL-33-dependent secretion of IL-13 from ILC2s is prevented by inhibition of the salt-inducible kinases (SIKs), as we have shown previously in mast cells (Darling NJ et al. , 2021, J. Biol. Chem. doi: 10.1016/j.jbc.2021.100428). We also report that a new SIK inhibitor with improved pharmacokinetic properties suppresses the recruitment of eosinophils to the lungs and serum immunoglobulin E (IgE) levels in the Alternaria alternata-induced model of allergic asthma. Our results suggest that drugs targeting SIK isoforms may have therapeutic potential for the treatment of asthma. ### Competing Interest Statement The authors have declared no competing interest. * BALF : bronchoalveolar lavage fluid BMMC : bone marrow-derived mast cells CCL : (C-C motif) ligand GM-CSF : granulocyte-macrophage colony stimulating factor IgE : immunoglobulin E IL : interleukin ILC2 : type 2 innate lymphoid cell PGE2 : prostaglandin E2 SIK : salt-inducible kinase TNF : tumour necrosis factor WT : wild type