The CD27-CD70 pathway and pathogenesis of autoimmune disease.

Abstract

To critically examine current evidence regarding the role of the CD27-CD70 pathway in the pathophysiology of autoimmune disease with a focus on understanding the contributions of this pathway as a potential new therapeutic target for systemic lupus erythematosus and rheumatoid arthritis. A PubMed search for articles was conducted using the following key words: ("CD27" OR "CD70") AND ("autoimmune disease" OR "systemic lupus erythematosus" OR "rheumatoid arthritis"). The search was limited to publications in English and included human and animal studies. The reference lists of identified articles were searched for further relevant citations. Publications on the list that was developed by this approach were assessed and those with relevance to CD27-CD70 pathway mediated pathophysiology in autoimmune disease were chosen for the detailed review. Data from human diseases and animal models document a major role for the CD27-CD70 receptor-ligand pair in providing signals that regulate T and B lymphocyte activation. The membrane receptor CD27 and its soluble form (sCD27) transmit co-stimulatory signals and induce activation and proliferation of T and B lymphocytes. CD70-expressing CD4 T lymphocytes are increased in autoimmune disease including systemic lupus erythematosus and rheumatoid arthritis and have been shown to produce pro-inflammatory cytokines. At the same time, preclinical evidence suggests that the outcome of CD27-CD70 signals may vary qualitatively between cell subsets and differentiation stages, especially for B lymphocytes. Blockade of the CD27-CD70 pathway has been shown to ameliorate disease manifestations in animal models including murine collagen-induced arthritis and experimental colitis. Current evidence from animal models and human diseases suggests that CD27-CD70 pathway contributes to the pathophysiology of autoimmunity. Although a number of basic questions still remain open, the available findings suggest that targeting the components of this pathway could provide useful and novel therapeutic interventions.