title: The myeloid receptor PILRβ mediates the balance of inflammatory responses through regulation of IL-27 production.
abstract: Paired immunoglobulin-like receptors beta, PILRβ, and alpha, PILRα, are related to the Siglec family of receptors and are expressed primarily on cells of the myeloid lineage. PILRβ is a DAP12 binding partner expressed on both human and mouse myeloid cells. The potential ligand, CD99, is found on many cell types, such as epithelial cells where it plays a role in migration of immune cells to sites of inflammation. Pilrb deficient mice were challenged with the parasite Toxoplasma gondii in two different models of infection induced inflammation; one involving the establishment of chronic encephalitis and a second mimicking inflammatory bowel disease in order to understand the potential role of this receptor in persistent inflammatory responses. It was found that in the absence of activating signals from PILRβ, antigen-presenting cells (APCs) produced increased amounts of IL-27, p28 and promoted IL-10 production in effector T cells. The sustained production of IL-27 led ultimately to enhanced survival after challenge due to dampened immune pathology in the gut. Similar protection was also observed in the CNS during chronic T. gondii infection after i.p. challenge again providing evidence that PILRβ is important for regulating aberrant inflammatory responses.
authors.affiliation: Merck Research Laboratories, Palo Alto, California, United States of America.
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Tato
authors.forename: Barbara
authors.initials: B
authors.lastname: Joyce-Shaikh
authors.forename: Antara
authors.initials: A
authors.lastname: Banerjee
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.forename: Manjiri
authors.initials: M
authors.lastname: Sathe
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Ewald
authors.forename: Man-Ru
authors.initials: MR
authors.lastname: Liu
authors.forename: Daniel
authors.initials: D
authors.lastname: Gorman
authors.forename: Terrill K
authors.initials: TK
authors.lastname: McClanahan
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Phillips
authors.forename: Paul G
authors.initials: PG
authors.lastname: Heyworth
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Cua
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004660:Encephalitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014122:Toxoplasma / Q000276:immunology; D014124:Toxoplasmosis, Animal / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: C486767:Il27 protein, mouse; D007378:Interleukins; C548038:PILRbeta protein, mouse; D011971:Receptors, Immunologic; D007371:Interferon-gamma