Anti-CXCR3 Antibody Suppresses Inflammation in C Protein-Induced Myositis Model

Ji Yong Choi¹, Joo Youn Lee², Ji Soo Park³, Sehui Shon³, Kathleen Phillips⁴, Eun Young Lee¹, Eun Bong Lee¹ and Yeong Wook Song^3,5, ¹Division of Rheumatology, Department of Internal Medicine, Seoul National University, Seoul, Korea, Republic of (South), ²Department of Molecular medicine and biopharmaceutical science, Seoul National University, seoul, Korea, Republic of (South), ³Department of Molecular medicine and biopharmaceutical science, Seoul National University, Seoul, Korea, Republic of (South), ⁴Pfizer Inc. Cambridge, MA. USA, Cambridge, MA, ⁵Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea, Republic of (South)

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Animal models, chemokines, Myositis, polymyositis and therapeutic targeting

Session Information

Date: Tuesday, November 7, 2017

Title: Muscle Biology, Myositis and Myopathies Poster

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: CXCR3 is a chemokine receptor that plays an important role in T cell chemotaxis in human autoimmune diseases. CXCR3, which is activated by ligand interferon gamma-inducible protein 10 (CXCL10, IP-10), was reported to be increased in muscle tissue in polymyositis. We investigated the effect of CXCR3 blockade in C protein-induced myositis (CIM) animal model.

Methods: CIM was induced with human skeletal C protein in 7 week old female C57BL/6 mice. Mice were treated with anti-CXCR3 antibody or control IgG at day 8 and day 15 after induction with C protein. Mouse muscle tissue was evaluated on day 21. H&E stain of muscle was performed to evaluate infiltrated inflammatory cells. CXCR3 expressing cells from mouse splenocytes and lymph node cells were analyzed by flow cytometry.

Results: Flow cytometric analysis demonstrated decreased CXCR3⁺CD8⁺memory T cells and CXCR3⁺pDC cells in lymph nodes of the anti-CXCR3 antibody treated group compared to that of the control IgG treated group (36.583 ± 9.39 % vs 31.266 ± 7.78 % ; p = 0.06, 40.6 ± 5.622 % vs 56.1 ± 5.72 % ; p = 0.012, respectively). In addition, CD8⁺IFN-γ⁺CXCR3⁺ cells in lymph nodes significantly decreased in the anti-CXCR3 antibody group compared to that of the vehicle group (9.725 ± 0.67 % vs 17.05 ± 4.69 % ; p < 0.01). Anti-CXCR3 antibody group showed lower inflammation score in muscle compared to that of the vehicle group (p = 0.032).

Conclusion: CXCR3 blockade suppressed inflammation in muscle and CXCR3 expression in lymph node cells in CIM model. These results suggest a therapeutic effect of anti-CXCR3 antibody in inflammatory myopathy.

onflicts of Interest (COI) declaration: Anti-CXCR3 antibody and control IgG antibody were provided by Pfizer through collaboration with Charles MacKay and Remy Robert at Monash Univeristy, Melbourne, Australia.

Disclosure: J. Y. Choi, None; J. Y. Lee, None; J. S. Park, None; S. Shon, None; K. Phillips, Pfizer Inc, 4; E. Y. Lee, None; E. B. Lee, None; Y. W. Song, None.

To cite this abstract in AMA style:

Choi JY, Lee JY, Park JS, Shon S, Phillips K, Lee EY, Lee EB, Song YW. Anti-CXCR3 Antibody Suppresses Inflammation in C Protein-Induced Myositis Model [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/anti-cxcr3-antibody-suppresses-inflammation-in-c-protein-induced-myositis-model/. Accessed .

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