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

Silvia Piconese1, Massimo Costanza, Claudio Tripodo

  • 1Molecular Immunology Unit, Department of Experimental Oncology and Molecular Medicine, AmadeoLab, Fondazione IRCCS Istituto Nazionale Tumori, via Amadeo 42, 20133 Milan, Italy.

Journal of Autoimmunity
|October 4, 2011
PubMed

Insights

Secreted protein acidic and rich in cysteine (SPARC) is crucial for germinal center formation and T helper 17 (Th17) cell differentiation during immune responses. SPARC optimizes interactions between follicular dendritic cells, B cells, and Th17 cells in lymph nodes.

Area of Science:

  • Immunology
  • Cell Biology
  • Extracellular Matrix Biology

Background:

  • Lymph node swelling involves dynamic extracellular matrix remodeling during immune responses.
  • The role of SPARC in regulating lymph node architecture and immune cell interactions is not fully understood.

Purpose of the Study:

  • To investigate the function of SPARC in germinal center formation and T helper 17 (Th17) cell differentiation.
  • To elucidate the role of SPARC in the crosstalk between follicular dendritic cells (FDCs), B cells, and Th17 cells.

Main Methods:

  • Analysis of SPARC expression in murine and human reactive lymph nodes.
  • Assessment of germinal center formation and humoral autoimmunity in SPARC-deficient mice.
  • Evaluation of Th17 cell differentiation and experimental autoimmune encephalomyelitis (EAE) development in SPARC-deficient models.
  • In vivo studies to identify SPARC-producing cells.

Main Results:

  • SPARC is expressed in germinal centers of reactive lymph nodes.
  • SPARC-deficient mice exhibit delayed germinal center arrangement, impaired FDC networking, and development of humoral autoimmunity linked to Th17 development.
  • SPARC is essential for optimal Th17 cell differentiation and EAE development.
  • Both radioresistant cells (FDCs) and CD4+ cells are sources of SPARC in vivo.
  • Th17 cell entry into germinal centers is dependent on SPARC.

Conclusions:

  • SPARC plays a critical role in optimizing lymphoid extracellular matrix changes, facilitating functional crosstalk between FDCs, B cells, and Th17 cells.
  • SPARC is indispensable for efficient germinal center formation and Th17 cell differentiation, impacting humoral immunity and autoimmune responses.

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