Therapeutic IDO2 antibody inhibits arthritis by blocking interaction between IDO2 and binding partner Runx1

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B635
Abstract ID: 4404

Presenting Author:
Lauren M.F. Merlo , Research Assistant Professor at Lankenau Inst. for Med. Res., Maine Line Hlth.

Abstract:

The enzyme indoleamine 2,3-dioxygenase 2 (IDO2) has been identified as an immune modulator that acts directly in B cells to promote autoimmunity in multiple model systems, thus making this protein a potential target for autoimmune therapy. To this end, we have developed an anti-IDO2 antibody that is able to directly inhibit the development and severity of autoimmune arthritis in murine models. This antibody successfully targets the intracellular protein IDO2 by internalizing, but not signaling, via FcγRIIb-receptor mediated endocytosis. Once inside the cell, the mechanism by which the antibody acts to reduce arthritis is unknown. Recently, we have discovered that IDO2 drives arthritis through a Runx1-mediated pathway in the KRN model of autoimmune arthritis. In vitro binding experiments have subsequently demonstrated that the IDO2 antibody disrupts the interaction between IDO2 and Runx1, thus providing a potential mechanism by which the anti-IDO2 Ig ameliorates arthritis. To confirm this result, we have used the anti-IDO2 Ig in the KRN model of arthritis on a genetic background lacking Runx1 in B cells. These experiments reveal that IDO2 Ig requires Runx1 for its in vivo function. Thus, the therapeutic IDO2 antibody can successfully internalize into cells and acts to inhibit arthritis by affecting the interaction between IDO2 and Runx1.