The matricellular protein SPARC supports follicular dendritic cell networking toward Th17 responses

Silvia Piconese, Massimo Costanza, Claudio Tripodo, Sabina Sangaletti, Silvia Musio, Paola Pittoni, Pietro L. Poliani, Alessia Burocchi, Alfonso L. Passafaro, Andrea Gorzanelli, Caterina Vitali, Claudia Chiodoni, Vincenzo Barnaba, Rosetta Pedotti, Mario P. Colombo

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)300-310
Number of pages11
JournalJournal of Autoimmunity
Volume37
Issue number4
DOIs
Publication statusPublished - Dec 2011

Keywords

  • Autoimmune diseases
  • Extracellular matrix
  • Germinal centre reaction
  • Th17 cells

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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    Piconese, S., Costanza, M., Tripodo, C., Sangaletti, S., Musio, S., Pittoni, P., Poliani, P. L., Burocchi, A., Passafaro, A. L., Gorzanelli, A., Vitali, C., Chiodoni, C., Barnaba, V., Pedotti, R., & Colombo, M. P. (2011). The matricellular protein SPARC supports follicular dendritic cell networking toward Th17 responses. Journal of Autoimmunity, 37(4), 300-310. https://doi.org/10.1016/j.jaut.2011.09.002