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Updated: May 28, 2026

Study of Dendritic Cell Development by Short Hairpin RNA-Mediated Gene Knockdown in a Hematopoietic Stem and Progenitor Cell Line In vitro
Published on: March 7, 2022
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.
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.
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.
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