MHC-compatible bone marrow stromal/stem cells trigger fibrosis by activating host T cells in a scleroderma mouse...

Area of Science:

• Immunology
• Autoimmune Diseases
• Fibrosis Research

Background:

• Systemic autoimmune diseases, such as scleroderma, are characterized by organ fibrosis.
• The precise mechanisms initiating fibrosis in these conditions remain incompletely understood.

Purpose of the Study:

• To investigate the role of bone marrow stromal/stem cells (BMSCs) in the pathogenesis of fibrosis in a mouse model of scleroderma.
• To determine if minor antigen mismatched BMSCs can trigger autoimmune responses and fibrosis.

Main Methods:

• Utilized a scleroderma mouse model for BMSC transplantation studies.
• Employed flow cytometry to analyze cell populations (PDGFRα(+), Sca-1(+), MHC class II, FOXP3(+), CD25(+)).
• Conducted in vitro T cell proliferation and cytokine secretion assays (IL-6).
• Utilized RAG2 knock out mice and adoptive T cell transfer experiments.

Main Results:

• Transplantation of MHC compatible, minor antigen mismatched BMSCs induced fibrosis in mice.
• Donor BMSCs expressed MHC class II post-transplantation, activating host T cells and decreasing regulatory T cells (Tregs).
• Mismatched BMSCs stimulated T cell proliferation and IL-6 secretion in vitro.
• Fibrosis occurred independently of donor T cells, and the autoimmune phenotype persisted after adoptive transfer of effector T cells.

Conclusions:

• Minor antigen mismatched BMSCs are key initiators of systemic fibrosis in this scleroderma model.
• The autoimmune response, once triggered by BMSCs, becomes independent of the initial donor cells.
• These findings suggest BMSCs as a potential therapeutic target for autoimmune fibrosis.