ILDR2 Is a Novel B7-like Protein That Negatively Regulates T Cell Responses

  • J Immunol. 2018 Mar 15;200(6):2025-2037. doi: 10.4049/jimmunol.1700325.
Iris Hecht  1 ,  Amir Toporik  2 ,  Joseph R Podojil  3  4 ,  Ilan Vaknin  2 ,  Gady Cojocaru  2 ,  Anat Oren  2 ,  Elizabeta Aizman  2 ,  Spencer C Liang  5 ,  Ling Leung  5 ,  Yosef Dicken  2 ,  Amit Novik  2 ,  Nadav Marbach-Bar  2 ,  Aziza Elmesmari  6 ,  Clare Tange  6 ,  Ashley Gilmour  6 ,  Donna McIntyre  6 ,  Mariola Kurowska-Stolarska  6 ,  Kay McNamee  7 ,  Judith Leitner  8 ,  Shirley Greenwald  2 ,  Liat Dassa  2 ,  Zurit Levine  2 ,  Peter Steinberger  8 ,  Richard O Williams  7 ,  Stephen D Miller  3  4 ,  Iain B McInnes  6 ,  Eyal Neria  2 ,  Galit Rotman  2
Affiliations
  • 1. Compugen Ltd., Holon 5885849, Israel; [email protected].
  • 2. Compugen Ltd., Holon 5885849, Israel.
  • 3. Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
  • 4. Interdepartmental Immunobiology Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
  • 5. Compugen USA Inc., South San Francisco, CA 94080.
  • 6. Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, United Kingdom.
  • 7. Kennedy Institute, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7FY, United Kingdom; and.
  • 8. Division of Immune Receptors and T Cell Activation, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria.
PMID: 29431694 DOI: 10.4049/jimmunol.1700325
Abstract

The B7-like protein family members play critical immunomodulatory roles and constitute attractive targets for the development of novel therapies for human diseases. We identified Ig-like domain-containing receptor (ILDR)2 as a novel B7-like protein with robust T cell inhibitory activity, expressed in immune cells and in immune-privileged and inflamed tissues. A fusion protein, consisting of ILDR2 extracellular domain with an Fc fragment, that binds to a putative counterpart on activated T cells showed a beneficial effect in the collagen-induced arthritis model and abrogated the production of proinflammatory cytokines and chemokines in autologous synovial-like cocultures of macrophages and cytokine-stimulated T cells. Collectively, these findings point to ILDR2 as a novel negative regulator for T cells, with potential roles in the development of immune-related diseases, including autoimmunity and Cancer.