title: Effect of immunoglobin-like transcript 7 cross-linking on plasmacytoid dendritic cells differentiation into antigen-presenting cells.
abstract: Plasmacytoid dendritic cells (pDC) are innate immunity effector cells which play a critical role in the transition from innate to adaptive immune response. Circulating blood pDC present an immature phenotype and can differentiate into either antigen-presenting cells (APC) or type I interferon (IFN-I)-producing cells (IPC). The immunoglobulin-like transcript (ILT)7 is a surface receptor expressed by immature pDC, and ILT7 cross-linking (XL-ILT7) inhibits IFN-I production by pDC in response to toll-like receptor (TLR)7 and 9 stimulation. We used peripheral blood mononuclear cells (PBMC) from healthy donors to test the effect of XL-ILT7 on 1) TLR7/9-mediated regulation of gut mucosal (α4β7 integrin) and lymph node (CCR7) migration markers; and 2) the maturation of pDC into APC. We found that XL-ILT7 mitigated the upregulation of CCR7 and enhanced that of β7 on TLR7/9-stimulated pDC. TLR7/9 stimulation induced upregulation of CD40, CD80 and CD86. CD40 expression was partially reduced by XL-ILT7, whereas CD86 was further enhanced. Plasmacytoid DC stimulated with TLR9 ligand in presence of XL-ILT7 retained the ability to induce T cell proliferation and activation in response to staphylococcal enterotoxin B (SEB) in pDC-T cell co-cultures. Our results suggest that XL-ILT7 favours the differentiation of immature pDC into APC rather than IPC.
authors.affiliation: Immunology Section, Chelsea and Westminster Hospital, Imperial College, London, United Kingdom.
authors.forename: Barbara
authors.initials: B
authors.lastname: Tavano
authors.affiliation: Immunology Section, Chelsea and Westminster Hospital, Imperial College, London, United Kingdom.
authors.forename: Adriano
authors.initials: A
authors.lastname: Boasso
mesh_terms: D000938:Antigen-Presenting Cells / Q000166:cytology*; D002454:Cell Differentiation / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear; D054400:Receptors, CCR7 / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology*; D018709:Statistics, Nonparametric; D051199:Toll-Like Receptor 7 / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism
chemical_list: C515370:CCR7 protein, human; C488262:LILRA4 protein, human; D054400:Receptors, CCR7; D011971:Receptors, Immunologic; C495348:TLR7 protein, human; C495371:TLR9 protein, human; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9