Systemic sclerosis (SSc) is an autoimmune disease in which vascular damage and immune activation leads to excessive accumulation of extracellular matrix in the skin and internal organs. Although the focus has been on adaptive immunity in SSc, recent data suggest that innate immunity is critically important. The innate immune system, the first-line barrier against pathogens, modulates mechanisms which activate adaptive immunity. Dysregulation of the innate immune system and toll-like receptors (TLRs) may link immune abnormalities and fibrosis in SSc. TLR signalling pathways might induce production of Type I interferon (IFN) and other cytokines, and represent one of the mechanisms that initiate and develop autoimmunity and subsequent fibrosis. Vitamin D displays many immunomodulatory effects on both innate and adaptive immune responses. Active vitamin D will produce signals via vitamin D receptor and influences TLR stimulation, IFN response, and antimicrobial peptide production. Vitamin D deficiency has been associated with many autoimmune disorders, and can influence clinical phenotype and immune disorders in SSc patients.
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