Ibrutinib enhances IL-17 response by modulating the function of bone marrow derived dendritic cells

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Ibrutinib (PCI-32765) is an irreversible dual Btk/Itk inhibitor shown to be effective in treating several B cell malignancies. However, limited studies have been conducted to study the effect of this drug on myeloid cell function. Hence, we studied the effect of ibrutinib treatment on TLR-4 mediated activation of bone marrow derived dendritic cell culture (DCs). Upon ibrutinib treatment, LPS-treated DCs displayed lower synthesis of TNF-α and nitric oxide and higher induction of IL-6, TGF-β and IL-18. While ibrutinib dampened MHC-II and CD86 expression on DCs, CD80 expression was upregulated. Further, ibrutinib-treated DCs promoted T cell proliferation and enhanced IL-17 production upon co-culture with nylon wool enriched T cells. Taken together, our results indicate that ibrutinib modulates TLR-4 mediated DC activation to promote an IL-17 response. We describe a novel mode of action for ibrutinib on DCs which should be explored to treat other forms of cancer besides B cell malignancies.


Biological Sciences: 2nd Place (The Ohio State University Edward F. Hayes Graduate Research Forum).
This is an Accepted Manuscript of an article published by Taylor & Francis Group in OncoImmunology on 06/09/2015, available online: http://www.tandfonline.com/10.1080/2162402X.2015.1057385


Ibrutinib, dendritic cells, TLR-4, T cells, IL-17, Btk


Natarajana, Gayathri, Cesar Terrazasb, Steve Oghumuc, Sanjay Varikutib, Jason A. Dubovskyd, John C. Byrdef and Abhay R. Satoskar. "Ibrutinib enhances IL-17 response by modulating the function of bone marrow derived dendritic cells." OncoImmunology. Accepted author version posted online: 09 Jun 2015. DOI: 10.1080/2162402X.2015.1057385