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

Abstract

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.

Serum Amyloid P Contained in Alveolar Fluid From Patients With Acute Respiratory Distress Syndrome Mediates the Inhibition of Monocyte Differentiation into Fibrocyte

“…4, Supplemental Digital Content 5, http://links.lww.com/ CCM/B688). Several studies also suggest a strong link between inflammation and fibrocyte differentiation (13,(29)(30)(31). Concordantly, we demonstrated that exposition of monocytes to corticosteroids in vivo or in vitro completely inhibited their (Fig.…”

TSH-Mediated TNFα Production in Human Fibrocytes Is Inhibited by Teprotumumab, an IGF-1R Antagonist

“…Fibrocytes migrate to sites of tissue injury in response to chemokines [1, 6, 7] and regulate site-specific inflammation and fibrosis through antigen-specific T cell stimulation [8], cytokine production [9], extracellular matrix remodeling [10], and differentiation into other cell types such as adipocytes and myofibroblasts [11, 12]. Fibrocytes have been implicated in a myriad of inflammatory and fibrotic conditions in the lung [2, 3, 7, 13], liver [14], kidney [15], heart [16], vasculature [17, 18], joints [19], and skin [20, 21]. Accumulating evidence suggests that they also play an important role in the pathogenesis of Graves disease (GD) and Graves orbitopathy (GO).…”

Rapamycin Blocks Fibrocyte Migration and Attenuates Bronchiolitis Obliterans in a Murine Model

“…Fibrocytes are bone marrow derived progenitor cells with the ability to differentiate down mesenchymal cell lineages [3–5]. They have been implicated in many pathologic processes of chronic inflammation and fibrosis, including arthritis, chronic kidney disease, scleroderma, asthma, and idiopathic pulmonary fibrosis [3, 4, 6–8]. They originate in bone marrow, mobilize into the circulation in response to inflammatory chemokines, and home to sites of inflammation.…”