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Small molecule CXCR3 antagonist NIBR2130 has only a limited impact on type 1 diabetes in a virus-induced mouse model

Christen, Selina and Holdener, Martin and Beerli, Christian and Thoma, Gebhard and Bayer, Monika and Pfeilschifter, Josef and Hintermann, Edith and Zerwes, Hans-Guenter and Christen, Urs (2011) Small molecule CXCR3 antagonist NIBR2130 has only a limited impact on type 1 diabetes in a virus-induced mouse model. Clinical and experimental immunology, 165 (3). pp. 318-328. ISSN 0009-9104

Abstract

CXCL10 is one of the key chemokines involved in trafficking of autoaggressive T cells to the islets of Langerhans during the autoimmune destruction of beta cells in type 1 diabetes (T1D). Blockade of CXCL10 or genetic deletion of its receptor CXCR3 results in a reduction of T1D in animal models. As an alternative to the use of neutralizing monoclonal antibodies to CXCL10 or CXCR3 we evaluated the small molecule CXCR3 antagonist NIBR2130 in a virus-induced mouse model for T1D. We found that the onset of T1D was significantly delayed in mice administered with NIBR2130. However, the observed protection was not stable over time since the mice turned diabetic upon removal of the antagonist. Despite the delay in T1D onset no significant differences in the islet infiltration rate and the frequency and activity of islet antigen-specific T cells between protected mice administered with NIBR2130 and control mice was found. Our data indicate that in contrast to direct inhibition of CXCL10, blockade of CXCR3 with the small molecule antagonist NIBR2130 has only a minor impact on trafficking and/or activation of autoaggressive T cells and is not sufficient to prevent T1D.

Item Type: Article
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Additional Information: author can archive post-print (ie final draft post-refereeing); On personal web site or secure external website at authors institution; Publisher's version/PDF cannot be used
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Date Deposited: 13 Oct 2015 13:15
Last Modified: 13 Oct 2015 13:15
URI: https://oak.novartis.com/id/eprint/3862

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