Abstract
Nanobody against V-set and Ig domain-containing 4 (Vsig4) on tissue macrophages, such as synovial macrophages, could visualize joint inflammation in multiple experimental arthritis models via single-photon emission computed tomography imaging. Here, we further addressed the specificity and assessed the potential for arthritis monitoring using near-infrared fluorescence (NIRF) Cy7-labeled Vsig4 nanobody (Cy7-Nb119). In vivo NIRF-imaging of collagen-induced arthritis (CIA) was performed using Cy7-Nb119. Signals obtained with Cy7-Nb119 or isotope control Cy7-NbBCII10 were compared in joints of naive mice versus CIA mice. In addition, pathological microscopy and fluorescence microscopy were used to validate the arthritis development in CIA. Cy7-Nb119 accumulated in inflamed joints of CIA mice, but not the naive mice. Development of symptoms in CIA was reflected in increased joint accumulation of Cy7-Nb119, which correlated with the conventional measurements of disease. Vsig4 is co-expressed with F4/80, indicating targeting of the increasing number of synovial macrophages associated with the severity of inflammation by the Vsig4 nanobody. NIRF imaging with Cy7-Nb119 allows specific assessment of inflammation in experimental arthritis and provides complementary information to clinical scoring for quantitative, non-invasive and economical monitoring of the pathological process. Nanobody labelled with fluorescence can also be used for ex vivo validation experiments using flow cytometry and fluorescence microscopy.
Highlights
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by a failure of spontaneous resolution of inflammation [1]
We confirmed that V-set and Ig domain-containing 4 (Vsig4)-specific nanobody targeting synovial macrophages constitutes a specific tool for non-invasive SPECT/CT imaging as a way of detecting early signs of inflammation and assessing inflammation in multiply arthritis models in vivo [26,27]
We wanted to assess the ability of the Vsig4 nanobody to act as an optical probe for near-infrared fluorescence (NIRF) imaging
Summary
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by a failure of spontaneous resolution of inflammation [1]. An increased number of sublining macrophages in the synovium is a sign of early onset of active rheumatic disease. The degree of synovial macrophage infiltration highly correlates with the degree of inflammatory lesion and joint erosion. The depletion of these macrophages from inflamed joints benefits the RA therapy. Some results in mouse models of arthritis have contributed to our understanding of the properties of synovial macrophages, the heterogeneous populations of immune cells in RA have not been fully characterized. Good markers to discriminate these resident macrophage populations could lead to monitoring of pro- or anti-inflammatory properties of these macrophage populations that inform future therapeutic strategies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
