Protein Tyrosine Phosphatase PTPRS Is an Inhibitory Receptor on Human and Murine Plasmacytoid Dendritic Cells

Immunity. 2015 Aug 18;43(2):277-88. doi: 10.1016/j.immuni.2015.07.009.

Anna Bunin ¹, Vanja Sisirak ², Hiyaa S Ghosh ³, Lucja T Grajkowska ², Z Esther Hou ³, Michelle Miron ³, Cliff Yang ³, Michele Ceribelli ⁴, Noriko Uetani ⁵, Laurence Chaperot ⁶, Joel Plumas ⁶, Wiljan Hendriks ⁷, Michel L Tremblay ⁵, Hans Häcker ⁸, Louis M Staudt ⁴, Peter H Green ⁹, Govind Bhagat ¹⁰, Boris Reizis ¹¹

Affiliations

1 Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA; Celiac Disease Center, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.
2 Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA; Department of Pathology and Department of Medicine, New York University Langone Medical Center, New York, NY 10016, USA.
3 Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA.
4 Lymphoid Malignancy Branch, Center for Cancer Research, National Cancer Institute, Rockville, MD 20852, USA.
5 Goodman Cancer Centre, McGill University, Montreal, Quebec H3A 1A3, Canada.
6 R&D Laboratory, EFS Rhone-Alpes Grenoble, La Tronche F-38701, France.
7 Department of Cell Biology, Radboud University, 6525 GA Nijmegen Medical Center, Nijmegen, The Netherlands.
8 Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
9 Celiac Disease Center, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.
10 Celiac Disease Center, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA; Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA.
11 Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032, USA; Department of Pathology and Department of Medicine, New York University Langone Medical Center, New York, NY 10016, USA. Electronic address: boris.reizis@nyumc.org.

PMID: 26231120 DOI: 10.1016/j.immuni.2015.07.009

Abstract

Plasmacytoid dendritic cells (pDCs) are primary producers of type I interferon (IFN) in response to viruses. The IFN-producing capacity of pDCs is regulated by specific inhibitory receptors, yet none of the known receptors are conserved in evolution. We report that within the human immune system, receptor protein tyrosine Phosphatase sigma (PTPRS) is expressed specifically on pDCs. Surface PTPRS was rapidly downregulated after pDC activation, and only PTPRS(-) pDCs produced IFN-α. Antibody-mediated PTPRS crosslinking inhibited pDC activation, whereas PTPRS knockdown enhanced IFN response in a pDC cell line. Similarly, murine Ptprs and the homologous receptor Phosphatase Ptprf were specifically co-expressed in murine pDCs. Haplodeficiency or DC-specific deletion of Ptprs on Ptprf-deficient background were associated with enhanced IFN response of pDCs, leukocyte infiltration in the intestine and mild colitis. Thus, PTPRS represents an evolutionarily conserved pDC-specific inhibitory receptor, and is required to prevent spontaneous IFN production and immune-mediated intestinal inflammation.

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