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. 2019 Sep 4;10:2019. doi: 10.3389/fimmu.2019.02019

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Copyright © 2019 Lin, Xu, Austin, Caplazi, Senger, Sun, Jeet, Young, Delarosa, Suto, Huang, Zhang, Yan, Corzo, Barck, Rajan, Looney, Gandham, Lesch, Liang, Mai, Ngu, Ratti, Chen, Misner, Lin, Danilenko, Katavolos, Doudemont, Uppal, Eastham, Mak, de Almeida, Bao, Hadadianpour, Keir, Carano, Diehl, Xu, Wu, Weimer, DeVoss, Lee, Balazs, Walsh, Alatsis, Martin and Zarrin.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Reduced induced or spontaneous mouse arthritis treated with aCSF1 and/or IL34. (A) Reduced longitudinal clinical score in CIA. DBA/1J mice were randomized at day 24 and then treated with aIL34 and/or aCSF1 for 7 weeks. Murine TNFRII-Fc decoy was used as a standard of care control. Isotype control includes anti-ragweed (aRW). Mice were examined weekly for joint inflammation in each paw. (B) Joint cortical bone volume (JCBV) determined by micro-CT (μCT) was used to quantify bone remodeling at the base of metatarsal bones. One hundred percent bone volume was set for naive mice. Anti-RW control group had lowest JCBV (average 79%) due to the bone erosion. TNFRII-Fc improved it to 87% and aIL34 to 84%. aCSF1 or dual aCSF1/aIL34 maintained the bone volume at a healthy level (106 and 104%). (C) Cartilage injury histology score (n = 38–40/group). (D) Analysis of cartilage damage by contrast-enhanced μCT imaging. Representative micro-CT images shows cartilage as dark rim at joint surface (left set of images). The cartilage scoring system employed a score range from 0 to 4 with the following scale: 0—thick continuous, 1—thick discontinuous, 2—thin continuous, 3—thin discontinuous, 4—no cartilage. All the five MTP joints were individually scored and averaged to get the total score per paw. The total cartilage score per mouse was obtained by averaging the total scores of both the hind limb paws (n = 6 per group). Anti-CSF1 or anti-IL34 monotherapies were not tested in this study. (E) Joint inflammatory CD11b⁺F4/80⁺ macrophages are reduced with aCSF1/aIL34 treatment. Arthritic mice, with a disease score of 4, were randomized and received anti-IL34/anti-CSF1, aRW, or TNFRII-Fc for 7 days. Ankle joints were harvested and processed for FACS. Each data point represents samples pooled from three mice. (F) Reduced CD4 T central memory (TCM) and in draining lymph nodes. (G) TNFΔ^ARE spontaneous arthritis, anti-CSF1 significantly reduces clinical arthritis score. (H) TNFΔ^ARE arthritis paw lesion histology score is improved by aCSF1. (I) TNFΔ^ARE arthritis JCBV is improved with aCSF1. Data are displayed as mean ± SEM. ^*p < 0.05, ^**p < 0.01, ^***p < 0.001, ^****p < 0.0001.