Rheumatoid arthritis bone marrow environment supports Th17 response

Area of Science:

• Immunology
• Rheumatology
• Cell Biology

Background:

• Rheumatoid arthritis (RA) is a systemic autoimmune disease causing joint destruction and disability.
• Bone marrow (BM) plays a critical role in RA pathogenesis, with processes occurring outside the joint.
• Interleukin-17 (IL-17) is a pro-inflammatory cytokine implicated in RA bone destruction, but its role in BM is not well understood.

Purpose of the Study:

• To investigate the presence and role of Th17-related cytokines within the bone marrow of rheumatoid arthritis patients.
• To understand the biological mechanisms of IL-17 production in the RA bone marrow microenvironment.

Main Methods:

• Collected bone marrow samples from rheumatoid arthritis (RA) and osteoarthritis (OA) patients.
• Quantified levels of IL-17 variants (IL-17AF, IL-17AA, IL-17FF), IL-1β, IL-6, IL-23, TGF-β, and CCL20 using ELISA.
• Assessed IL-17-producing cells via flow cytometry and examined IL-17 production by BM mononuclear cells stimulated with IL-15 in vitro.

Main Results:

• Elevated levels of IL-17AF, IL-1β, IL-6, and CCL20 were found in RA BM plasma compared to OA.
• Significantly higher percentages of IL-17-producing T helper cells (CD3+CD4+IL-17+ and CD3+CD4+IL-17+IFN-γ+) were observed in RA BM.
• Interleukin-15 (IL-15), abundant in RA BM, stimulated increased IL-17 production from cultured BM mononuclear cells.

Conclusions:

• The bone marrow microenvironment in RA promotes Th17 cell responses.
• Overproduction of IL-17AF in RA bone marrow contributes to increased inflammation and tissue destruction.
• These findings highlight the bone marrow as a key site for IL-17-mediated pathology in rheumatoid arthritis.