title: The immune inhibitory receptor LAIR-1 is highly expressed by plasmacytoid dendritic cells and acts complementary with NKp44 to control IFNα production.
abstract: Plasmacytoid dendritic cells (pDCs) are a subset of dendritic cells endowed with the capacity of producing large amounts of IFNα. Here we show that the Leukocyte-Associated Ig-like Receptor-1 (LAIR-1) is abundantly expressed on pDCs (the highest expression among all leukocytes) and its cross-linking inhibits IFNα production in response to Toll-like receptor ligands. Remarkably, LAIR-1 expression in pDCs is down-regulated in the presence of interleukin (IL)-3, thus indicating coordinated functions with NKp44, another pDC inhibitory receptor, which is conversely induced by IL-3. Nevertheless, the expression of NKp44 in pDCs isolated from secondary lymphoid organs, which is thought to be influenced by IL-3, is not coupled to a decreased expression of LAIR-1. Interestingly, pDCs isolated from peripheral blood of systemic lupus erithematosus (SLE) patients express lower levels of LAIR-1 while displaying slight but consistent expression of NKp44, usually undetectable on pDCs derived from healthy donors. Using sera derived from SLE patients, we show that LAIR-1 and NKp44 display synergistic inhibitory effects on IFNα production by interleukin IL-3 cultured pDCs stimulated with DNA immunocomplexes. In conclusion, our results indicate that the inhibitory function of LAIR-1 may play a relevant role in the mechanisms controlling IFNα production by pDCs both in normal and pathological innate immune responses.
authors.affiliation: Laboratory of Immunology and Biotherapy, Department of Human Pathology, University of Messina, Messina, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Bonaccorsi
authors.forename: Claudia
authors.initials: C
authors.lastname: Cantoni
authors.forename: Paolo
authors.initials: P
authors.lastname: Carrega
authors.forename: Daniela
authors.initials: D
authors.lastname: Oliveri
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Lui
authors.forename: Romana
authors.initials: R
authors.lastname: Conte
authors.forename: Michele
authors.initials: M
authors.lastname: Navarra
authors.forename: Riccardo
authors.initials: R
authors.lastname: Cavaliere
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Traggiai
authors.forename: Marco
authors.initials: M
authors.lastname: Gattorno
authors.forename: Alberto
authors.initials: A
authors.lastname: Martini
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Mingari
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretta
authors.forename: Guido
authors.initials: G
authors.lastname: Ferlazzo
mesh_terms: D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000235:genetics / Q000378:metabolism; D008221:Lymphoid Tissue / Q000378:metabolism; D055629:Natural Cytotoxicity Triggering Receptor 2 / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016898:Interferon-alpha; C112837:NCR2 protein, human; D055629:Natural Cytotoxicity Triggering Receptor 2; D011971:Receptors, Immunologic; C108073:leukocyte-associated immunoglobulin-like receptor 1