NDLI: Therapeutic antibody targeting of indoleamine-2,3-dioxygenase (IDO2) inhibits autoimmune arthritis.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Merlo, Lauren M. F. Grabler, Samantha DuHadaway, James B. Pigott, Elizabeth Manley, Kaylend Prendergast, George C. Laury-Kleintop, Lisa D. Mandik-Nayak, Laura
Description	Country affiliation: United States Author Affiliation: Merlo LM ( Lankenau Institute for Medical Research, 100 Lancaster Ave., Wynnewood, PA 19096, USA.); Grabler S ( Lankenau Institute for Medical Research, 100 Lancaster Ave., Wynnewood, PA 19096, USA.); DuHadaway JB ( Lankenau Institute for Medical Research, 100 Lancaster Ave., Wynnewood, PA 19096, USA.); Pigott E ( Lankenau Institute for Medical Research, 100 Lancaster Ave., Wynnewood, PA 19096, USA.); Manley K ( Lankenau Institute for Medical Research, 100 Lancaster Ave., Wynnewood, PA 19096, USA.); Prendergast GC ( Lankenau Institute for Medical Research, 100 Lancaster Ave., Wynnewood, PA 19096, USA); Laury-Kleintop LD ( Lankenau Institute for Medical Research, 100 Lancaster Ave., Wynnewood, PA 19096, USA.); Mandik-Nayak L ( Lankenau Institute for Medical Research, 100 Lancaster Ave., Wynnewood, PA 19096, USA. Electronic address: Mandik-NayakL@mlhs.org.)
Abstract	Rheumatoid arthritis (RA) is a debilitating inflammatory autoimmune disease with no known cure. Recently, we identified the immunomodulatory enzyme indoleamine-2,3-dioxygenase 2 (IDO2) as an essential mediator of autoreactive B and T cell responses driving RA. However, therapeutically targeting IDO2 has been challenging given the lack of small molecules that specifically inhibit IDO2 without also affecting the closely related IDO1. In this study, we develop a novel monoclonal antibody (mAb)-based approach to therapeutically target IDO2. Treatment with IDO2-specific mAb alleviated arthritis in two independent preclinical arthritis models, reducing autoreactive T and B cell activation and recapitulating the strong anti-arthritic effect of genetic IDO2 deficiency. Mechanistic investigations identified FcÎ³RIIb as necessary for mAb internalization, allowing targeting of an intracellular antigen traditionally considered inaccessible to mAb therapy. Taken together, our results offer preclinical proof of concept for antibody-mediated targeting of IDO2 as a new therapeutic strategy to treat RA and other autoantibody-mediated diseases.
File Format	HTM / HTML
ISSN	15216616
Journal	Clinical Immunology
Volume Number	179
e-ISSN	15217035
Language	English
Publisher	Elsevier
Publisher Date	2017-02-20
Publisher Place	United States
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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