Haiyan Liu1,2, Jin Zhao2, Min Su2,3, Xiaohong Tian4, Laijun Lai2,5. 1. Shandong Provincial Hospital, Shandong First Medical University, Jinan, China. 2. Department of Allied Health Sciences, University of Connecticut, Storrs, CT, USA. 3. Department of Human Histology and Embryology, Tissue Engineering and Stem Cell Research Center, Guizhou Medical University, Guiyang. 4. Department of Tissue Engineering, School of Fundamental Science, China Medical University, Shenyang, China. 5. University of Connecticut Stem Cell Institute, University of Connecticut, Storrs, CT, USA.
Abstract
OBJECTIVES: RA is a chronic autoimmune disease characterized by joint inflammation and tissue destruction. Immune responses mediated by T cells and autoantibodies are known to play critical roles in RA. Collagen type II (CII)-induced arthritis (CIA) is a commonly used animal model of human RA. We have previously reported the identification of a new T cell inhibitory molecule CD300c. Here we investigate the ability of recombinant CD300c-IgG2a Fc (CD300c-Ig) fusion protein to prevent and treat CIA. METHODS: Mice were induced to develop CIA by CII and injected with CD300c-Ig or control Ig protein before or after CIA symptoms occur. The mice were examined for CIA clinical and pathological scores, and analysed for the expression of proinflammatory cytokines, the percentage and activation of CD4 T cells and regulatory T cells, CII-specific T cell proliferation and cytokine production, and CII-specific autoantibody production. RESULTS: In a prevention model, CD300c-Ig significantly decreases CIA incidence, and reduces clinical and pathological arthritis scores. In the treatment model, CD300c-Ig ameliorates established CIA. The beneficial effects of CD300c-Ig are related to decreased expansion and activation of T cells in the spleen and reduced expression of proinflammatory cytokines in the joints. CD300c-Ig also inhibits CII-specific T cell proliferation and Th1 and Th17 cytokine production. In addition, CD300c-Ig treatment reduced the production of CII autoantibodies in the serum. Furthermore, CD300c-Ig inhibits the proliferation and activation of T cells from RA patients in vitro. CONCLUSION: CD300c-Ig protein has the potential to be used in the treatment of patients with RA.
OBJECTIVES: RA is a chronic autoimmune disease characterized by joint inflammation and tissue destruction. Immune responses mediated by T cells and autoantibodies are known to play critical roles in RA. Collagen type II (CII)-induced arthritis (CIA) is a commonly used animal model of human RA. We have previously reported the identification of a new T cell inhibitory molecule CD300c. Here we investigate the ability of recombinant CD300c-IgG2a Fc (CD300c-Ig) fusion protein to prevent and treat CIA. METHODS: Mice were induced to develop CIA by CII and injected with CD300c-Ig or control Ig protein before or after CIA symptoms occur. The mice were examined for CIA clinical and pathological scores, and analysed for the expression of proinflammatory cytokines, the percentage and activation of CD4 T cells and regulatory T cells, CII-specific T cell proliferation and cytokine production, and CII-specific autoantibody production. RESULTS: In a prevention model, CD300c-Ig significantly decreases CIA incidence, and reduces clinical and pathological arthritis scores. In the treatment model, CD300c-Ig ameliorates established CIA. The beneficial effects of CD300c-Ig are related to decreased expansion and activation of T cells in the spleen and reduced expression of proinflammatory cytokines in the joints. CD300c-Ig also inhibits CII-specific T cell proliferation and Th1 and Th17 cytokine production. In addition, CD300c-Ig treatment reduced the production of CII autoantibodies in the serum. Furthermore, CD300c-Ig inhibits the proliferation and activation of T cells from RA patients in vitro. CONCLUSION: CD300c-Ig protein has the potential to be used in the treatment of patients with RA.
Authors: Liqun Luo; Gefeng Zhu; Haiying Xu; Sheng Yao; Gang Zhou; Yuwen Zhu; Koji Tamada; Lanqing Huang; Andrew D Flies; Megan Broadwater; William Ruff; Jan M A van Deursen; Ignacio Melero; Zhou Zhu; Lieping Chen Journal: PLoS One Date: 2015-06-11 Impact factor: 3.240
Authors: Fan Zhang; Kevin Wei; Kamil Slowikowski; Chamith Y Fonseka; Deepak A Rao; Stephen Kelly; Susan M Goodman; Darren Tabechian; Laura B Hughes; Karen Salomon-Escoto; Gerald F M Watts; A Helena Jonsson; Javier Rangel-Moreno; Nida Meednu; Cristina Rozo; William Apruzzese; Thomas M Eisenhaure; David J Lieb; David L Boyle; Arthur M Mandelin; Brendan F Boyce; Edward DiCarlo; Ellen M Gravallese; Peter K Gregersen; Larry Moreland; Gary S Firestein; Nir Hacohen; Chad Nusbaum; James A Lederer; Harris Perlman; Costantino Pitzalis; Andrew Filer; V Michael Holers; Vivian P Bykerk; Laura T Donlin; Jennifer H Anolik; Michael B Brenner; Soumya Raychaudhuri Journal: Nat Immunol Date: 2019-05-06 Impact factor: 25.606
Authors: Weiqian Chen; Julie Wang; Zhenjian Xu; Feng Huang; Wenbin Qian; Jilin Ma; Hwa Bok Wee; Gregory S Lewis; Rayford R June; Peter H Schafer; Jin Lin; Song Guo Zheng Journal: Front Immunol Date: 2018-07-18 Impact factor: 7.561