Mechanistic insights into environmental and genetic risk factors for systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organ systems with diverse presentation, primarily affecting women of reproductive age. Various genetic and environmental risk factors are involved in the pathogenesis of SLE, and many SLE susceptibility genes have been identified recently; however, gene therapy is not a viable clinical option at this time. Thus, environmental risks factors, particularly regional characteristics that can be controlled, need to be further investigated. Here, we systematically explored these risk factors, including ultraviolet radiation, seasonal distribution, geographical distribution, and climate factors, and also summarized the mechanisms related to these risk factors. Probable mechanisms were explicated in at least four aspects including inflammatory mediators, apoptosis and autophagy in keratinocytes, epigenetic factors, and gene-environment interactions. This information is expected to provide practical insights into these risk factors in order to benefit patients with SLE and facilitate the development of potential therapeutic strategies.

Keywords: Risk factors; climate factors; geographical distribution; season distribution; systemic lupus erythematosus; ultraviolet radiation.

Figure 1

The role of UVR in the development of SLE. Abbreviation: SLE, systemic lupus erythematosus; UVR, ultraviolet radiation; IFN, interferon; IL, interleukin; TNF, tumor necrosis factor; CXCL, chemokine (C-X-C motif) ligand; CCL, chemokine (C-C motif) ligand; ICAM-1, intercellular adhesion molecule 1; HMGB1, high-mobility group protein B1; LFA-1, lymphocyte function-associated antigen; DNA methyl transferase 1, DNMT1.