title: Blocking of LFA-1 enhances expansion of Th17 cells induced by human CD14(+) CD16(++) nonclassical monocytes.
abstract: Among human peripheral blood (PB) monocyte (Mo) subsets, the classical CD14(++) CD16(-) (cMo) and intermediate CD14(++) CD16(+) (iMo) Mos are known to activate pathogenic Th17 responses, whereas the impact of nonclassical CD14(+) CD16(++) Mo (nMo) on T-cell activation has been largely neglected. The aim of this study was to obtain new mechanistic insights on the capacity of Mo subsets from healthy donors (HDs) to activate IL-17(+) T-cell responses in vitro, and assess whether this function was maintained or lost in states of chronic inflammation. When cocultured with autologous CD4(+) T cells in the absence of TLR-2/NOD2 agonists, PB nMos from HDs were more efficient stimulators of IL-17-producing T cells, as compared to cMo. These results could not be explained by differences in Mo lifespan and cytokine profiles. Notably, however, the blocking of LFA-1/ICAM-1 interaction resulted in a significant increase in the percentage of IL-17(+) T cells expanded in nMo/T-cell cocultures. As compared to HD, PB Mo subsets of patients with rheumatoid arthritis were hampered in their T-cell stimulatory capacity. Our new insights highlight the role of Mo subsets in modulating inflammatory T-cell responses and suggest that nMo could become a critical therapeutic target against IL-17-mediated inflammatory diseases.
authors: Department of Biomedicine (DBM), Basel University Hospital, Basel, Switzerland.
authors: Emmanuel
authors: E
authors: Traunecker
authors: Instituto Gulbenkian de Ciência, Oeiras, Portugal.|Unidade de Investigação em Reumatologia, Instituto de Medicina Molecular da Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.
authors: Rui
authors: R
authors: Gardner
authors: Rheumatology Department, Lisbon Academic Medical Centre, Lisbon, Portugal.
authors: João Eurico
authors: JE
authors: Fonseca
authors: Rheumatology Department, Lisbon Academic Medical Centre, Lisbon, Portugal.
authors: Joaquim
authors: J
authors: Polido-Pereira
authors: Universitätsklinik für Rheumatologie, Klinische Immunologie und Allergologie, Inselspital, Bern, Switzerland.
authors: Michael
authors: M
authors: Seitz
authors: Universitätsklinik für Rheumatologie, Klinische Immunologie und Allergologie, Inselspital, Bern, Switzerland.
authors: Peter M
authors: PM
authors: Villiger
authors: Department of Biomedicine (DBM), Cancer Immunotherapy, Institute of Surgical Research (ICFS), Basel University Hospital, Basel, Switzerland.
authors: Giandomenica
authors: G
authors: Iezzi
authors: Department of Biomedicine (DBM), Cancer Immunotherapy, Institute of Surgical Research (ICFS), Basel University Hospital, Basel, Switzerland.
authors: Elisabetta
authors: E
authors: Padovan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019138:Antibodies, Blocking / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001168:Arthritis / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000145:classification / Q000276:immunology*; D053473:Nod2 Signaling Adaptor Protein / Q000819:agonists; D017452:Receptors, IgG / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000037:antagonists & inhibitors; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000819:agonists
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D016207:Cytokines; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D020381:Interleukin-17; D018950:Lipopolysaccharide Receptors; D016169:Lymphocyte Function-Associated Antigen-1; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D017452:Receptors, IgG; D016201:Receptors, Lymphocyte Homing; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D018799:Intercellular Adhesion Molecule-1
keywords: LFA-1; Monocyte; Rheumatoid arthritis; TLR-2; Th17