title: The matricellular protein SPARC supports follicular dendritic cell networking toward Th17 responses.
abstract: Lymphnode swelling during immune responses is a transient, finely regulated tissue rearrangement, accomplished with the participation of the extracellular matrix. Here we show that murine and human reactive lymph nodes express SPARC in the germinal centres. Defective follicular dendritic cell networking in SPARC-deficient mice is accompanied by a severe delay in the arrangement of germinal centres and development of humoral autoimmunity, events that are linked to Th17 development. SPARC is required for the optimal and rapid differentiation of Th17 cells, accordingly we show delayed development of experimental autoimmune encephalomyelitis whose pathogenesis involves Th17. Not only host radioresistant cells, namely follicular dendritic cells, but also CD4(+) cells are the relevant sources of SPARC, in vivo. Th17 differentiation and germinal centre formation mutually depend on SPARC for a proper functional crosstalk. Indeed, Th17 cells can enter the germinal centres in SPARC-competent, but not SPARC-deficient, mice. In summary, SPARC optimizes the changes occurring in lymphoid extracellular matrix harboring complex interactions between follicular dendritic cells, B cells and Th17 cells.
authors.affiliation: Molecular Immunology Unit, Department of Experimental Oncology and Molecular Medicine, AmadeoLab, Fondazione IRCCS Istituto Nazionale Tumori, via Amadeo 42, 20133 Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Piconese
authors.forename: Massimo
authors.initials: M
authors.lastname: Costanza
authors.forename: Claudio
authors.initials: C
authors.lastname: Tripodo
authors.forename: Sabina
authors.initials: S
authors.lastname: Sangaletti
authors.forename: Silvia
authors.initials: S
authors.lastname: Musio
authors.forename: Paola
authors.initials: P
authors.lastname: Pittoni
authors.forename: Pietro L
authors.initials: PL
authors.lastname: Poliani
authors.forename: Alessia
authors.initials: A
authors.lastname: Burocchi
authors.forename: Alfonso L
authors.initials: AL
authors.lastname: Passafaro
authors.forename: Andrea
authors.initials: A
authors.lastname: Gorzanelli
authors.forename: Caterina
authors.initials: C
authors.lastname: Vitali
authors.forename: Claudia
authors.initials: C
authors.lastname: Chiodoni
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Barnaba
authors.forename: Rosetta
authors.initials: R
authors.lastname: Pedotti
authors.forename: Mario P
authors.initials: MP
authors.lastname: Colombo
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002450:Cell Communication / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D020566:Dendritic Cells, Follicular / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D056724:Immunity, Humoral / Q000235:genetics; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009103:Multiple Sclerosis / Q000276:immunology*; D009185:Myelin Proteins / Q000008:administration & dosage; D063308:Myelin-Oligodendrocyte Glycoprotein; D015676:Osteonectin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D015676:Osteonectin