Environmental factors and their regulation of immunity in multiple sclerosis

Abstract

Epidemiological and clinical studies have shown that environmental factors such as infections, smoking and vitamin D are associated with the risk of developing multiple sclerosis (MS). Some of these factors also play a role in the MS disease course. We are currently beginning to understand how environmental factors may impact immune function in MS on a cellular and molecular level. Here we review epidemiological, clinical and basic immunological studies on the environmental factors, viral and parasitic infections, smoking, and vitamin D and relate epidemiological findings with their likely pathophysiology in MS.

Fig. 1

Steps in the immunopathogenesis of MS and modulation by environmental factors. An initial activation of T cells by antigen presenting cells in the periphery , particularly in lymph nodes, leads to the increased generation of Th1 and/or Th17 pro-inflammatory subsets in MS. These cells, and other leukocyte subsets including monocytes and B cells, transit in blood where they can adhere onto inflamed endothelial cells (EC). Predominantly at post-capillary venules in the CNS, the leukocyte populations produce MMPs to invade across the glia limitans into the CNS parenchyma. T cells may undergo reactivation within the CNS and they, together with other leukocyte populations that have entered the CNS, contribute to tissue injury . This figure also displays where the environmental factors that influence MS may act in the cascade of immunopathogenesis.