Circulating fibrocytes contribute to the pathogenesis of collagen antibody-induced arthritis

Arthritis Rheum. 2012 Nov;64(11):3583-93. doi: 10.1002/art.34589.


Objective: Rheumatoid arthritis (RA) is a systemic autoimmune disease resulting in joint inflammation. Fibroblast-like synoviocytes in affected joints are responsible for pannus formation and cytokine/chemokine production, resulting in leukocyte recruitment and bone/cartilage destruction. Previously, we identified a multipotent stem cell population of activated fibrocytes in the blood of patients with RA that may have a role in disease pathogenesis, perhaps as fibroblast-like synoviocyte precursors. The aim of this study was to further characterize the contribution of circulating fibrocytes to the pathogenesis of RA.

Methods: Circulating fibrocytes were isolated from mice with collagen-induced arthritis and transferred intravenously into recipient mice with collagen antibody-induced arthritis (CAIA). The activation status of circulating fibrocytes was determined using multidimensional phosphoflow cytometric analysis of the signaling effectors STAT-5, STAT-1, AKT, and JNK. Circulating fibrocyte trafficking and matrix metalloproteinase (MMP) activity were assessed in real time using fluorescence molecular tomography, specifically labeling circulating fibrocytes with CellVue Maroon and measuring MMP activity using MMPSense 680.

Results: The numbers of circulating fibrocytes were increased early during the onset of CAIA, concomitant with their activation, as measured by phosphorylation of STAT-5. Adoptive transfer of circulating fibrocytes augmented disease scores and increased class II major histocompatibility complex expression and peripheral blood phosphoactivation profiles in recipient mice with CAIA. Notably, adoptively transferred fluorescence-labeled circulating fibrocytes rapidly migrated into the affected joints of recipient mice with CAIA, and this was associated with augmented neutrophil recruitment into affected joints and MMP activation.

Conclusion: Circulating fibrocytes migrate to joints and influence the onset of disease processes in arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / immunology*
  • Arthritis, Experimental / pathology*
  • Autoantibodies / immunology
  • Cell Movement / immunology
  • Cell Separation / methods
  • Disease Models, Animal
  • Disease Progression
  • Fibroblasts / immunology
  • Fibroblasts / pathology
  • Joints / immunology
  • Joints / pathology
  • Male
  • Matrix Metalloproteinases / metabolism
  • Mice
  • Mice, Inbred DBA
  • Multipotent Stem Cells / immunology*
  • Multipotent Stem Cells / pathology*
  • Multipotent Stem Cells / transplantation
  • Neutrophils / immunology
  • Neutrophils / pathology
  • Stem Cell Transplantation / methods
  • Synovial Membrane / immunology*
  • Synovial Membrane / metabolism
  • Synovial Membrane / pathology*


  • Autoantibodies
  • Matrix Metalloproteinases