Our studies have identified the involvement of Bruton’s tyrosine kinase (BTK) and IL-2 inducible T cell kinase (ITK) in both skin and lung GVHD, and demonstrated that treatment with Ibrutinib, an FDA-approved irreversible inhibitor of BTK and ITK, delayed progression, improved survival, and ameliorated clinical and pathological manifestations of chronic GVHD (cGVHD) (1). Although BTK inhibition has been shown to attenuate macrophage activation and inflammatory gene expression, the effects of Ibrutinib on monocyte and macrophage activation and differentiation during cGVHD has not been examined. This project will utilize our unique preclinical models of macrophage dependent skin and lung cGVHD to address this. These studies are aimed at increasing our understanding of the mechanisms by which Ibrutinib attenuates cGVHD and have the potential to identify new myeloid targets for the development of much needed novel and efficacious anti-fibrotic therapeutics.
(1) Dubovsky JA, et al. J Clin Invest. 2014;124(11):4867.