A Critical Epitope in CD147 Facilitates Memory CD4 T-cell Hyper-activation in Rheumatoid Arthritis

Overview

Journal Cell Mol Immunol

Date 2018 Mar 23

PMID 29563614

Citations 19

Authors

Na Guo

Sheng Ye

Kui Zhang

Xiaoling Yu

Hongyong Cui

Xiangmin Yang

Peng Lin

Minghua Lv

Jinlin Miao

Yang Zhang

Qing Han

Rongguang Zhang

Zhinan Chen

Ping Zhu

Affiliations

Soon will be listed here.

Abstract

The abnormal activation of CD4CD45RO memory T (Tm) cells plays an important role in the pathogenesis of rheumatoid arthritis (RA). Previous studies have shown that CD147 participates in T-cell activation. However, it remains unclear whether CD147 is involved in abnormal Tm-cell activation in RA patients. In this study, we demonstrated that CD147 was predominantly upregulated in Tm cells derived from RA patients. The anti-CD147 mAb 5A12 specifically inhibited Tm-cell activation and proliferation and further restrained osteoclastogenesis. Using a structural-functional approach, we depicted the interface between 5A12 and CD147. This allowed us to identify two critical residues, Lys63 and Asp65, as potential targets for RA treatment, as the double mutation K63A/D65A inhibited Tm-cell activation, mimicking the neutralization by 5A12. This study provides not only a theoretical basis for a "CD147-Tm/Osteoclast-RA chain" for the potential prevention and treatment of RA or other T-cell-mediated autoimmune diseases but also a new target for related drug design and development.

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