Chromosome Segregation Defects in Scleroderma

Abstract

Fibrosis in systemic sclerosis (SSc or scleroderma) is characterized by an abundance of chromosome segregation defects and chromosome instability (CIN) that lead to overactivation of autoimmunity and inflammation. This chapter will emphasize the most recent findings on the involvement of centromere and telomere dysfunction in scleroderma. We will discuss how centromere and telomere dysfunction contribute to CIN, fibrosis, and cellular autoimmunity in scleroderma. We will also summarize how chromosome segregation defects in the form of aneuploidy and micronuclei formation activate the Cyclic GMP–AMP synthase (cGAS) Stimulator of interferon genes (STING) pathway of cellular immunity. Activation of this pathway induces production of inflammatory cytokines IFNβ and IL6. Finally, we will summarize the most recent therapies to block the cGAS-STING pathway and treat fibrosis.