Immune-bone interplay in the structural damage in rheumatoid arthritis

Area of Science:

• Immunology
• Bone Biology
• Rheumatology

Background:

• The immune and skeletal systems closely interact to maintain homeostasis.
• Rheumatoid arthritis (RA) pathogenesis involves immune responses leading to osteoclast-mediated bone erosion.
• An imbalance between forkhead box protein 3 (Foxp3)⁺ regulatory T (Treg) cells and T helper type 17 (Th17) cells is implicated in autoimmune diseases like RA.

Purpose of the Study:

• To review recent advances in understanding the immune-bone interplay in arthritis-related bone destruction.
• To highlight the role of T cell subsets, particularly Th17 cells, in RA pathogenesis.
• To discuss the contribution of exFoxp3 Th17 cells and antibody modulation to osteoclastogenesis in arthritis.

Main Methods:

• Literature review of recent research on immune-bone interactions in arthritis.
• Analysis of the roles of Treg, Th17, and exFoxp3 Th17 cells in bone erosion.
• Examination of the mechanisms by which Th17 cells and antibodies contribute to osteoclastogenesis.

Main Results:

• Th17 cells promote bone destruction in arthritis by up-regulating RANKL and inducing inflammation.
• Pathogenic conversion of Foxp3⁺ T cells into exFoxp3 Th17 cells generates potent osteoclastogenic T cells.
• Th17 cells also influence arthritis pathogenesis through antibody production modulation, impacting osteoclastogenesis.

Conclusions:

• The interplay between immune cells and bone is critical in RA.
• Imbalances in T cell subsets, especially Th17 cells and their precursors, are central to bone erosion in arthritis.
• Understanding these immune-bone interactions offers insights into potential therapeutic targets for RA-induced bone loss.