Tissue-Engineered Stromal Reticula to Study Lymph Node Fibroblastic Reticular Cells in Type I Diabetes

Area of Science:

• Immunology
• Cell Biology
• Diabetes Research

Background:

• Fibroblastic reticular cells (FRCs) are crucial for lymph node (LN) structure and immune tolerance.
• In Type 1 diabetes (T1D), altered FRCs may impair the presentation of self-antigens to T cells, hindering tolerance.
• FRC network organization is vital for adaptive immunity.

Purpose of the Study:

• To engineer lymph node-like FRC reticula to investigate FRC alterations in T1D.
• To study the engagement of autoreactive T cells with FRCs in a 3D environment.

Main Methods:

• Characterized FRC networks in pancreatic and skin-draining LNs of non-obese diabetic (NOD) and resistant (NOR) mice.
• Cultured murine and human FRCs in collagen sponges to create 3D reticula.
• Co-cultured FRCs expressing T1D antigens with specific T cells in 2D and 3D scaffolds to assess T cell engagement.

Main Results:

• NOD mice exhibited larger reticular pores in LN FRC networks compared to NOR controls.
• NOD FRCs showed delayed remodeling in 3D scaffolds and reduced gp38 marker expression, which improved in 3D.
• FRC reticula expressing T1D antigens facilitated greater autoreactive T cell engagement than 2D cultures.

Conclusions:

• Developed engineered LN-like FRC reticula that mimic the organization and phenotype of FRCs in T1D LNs.
• These 3D models provide a platform for studying T1D-related tolerogenic autoreactive T cell engagement.