However, urbanization maintains exposure to the crowd infections that lack immunoregulatory roles, while accelerating loss of exposure to the natural environment. This effect is
most pronounced in individuals of low socioeconomic status (SES) Epigenetic Reader Domain inhibitor who lack rural second homes and rural holidays. Interestingly, large epidemiological studies indicate that the health benefits of living close to green spaces are most pronounced for individuals of low SES. Here we discuss the immunoregulatory role of the natural environment, and how this may interact with, and modulate, the proinflammatory effects of psychosocial stressors in low SES individuals. “
“Since their discovery as a distinct T helper (Th) cell lineage, Th17 cells have been extensively investigated both in mice and in humans. These studies have identified factors involved in their
differentiation and effector functions and have also revealed a high degree of flexibility that seems to be a characteristic of the Th17-cell lineage. In this review, we discuss recent studies addressing the heterogeneity of human Th17 cells, their differentiation requirements, their migratory capacities, and their role in defense against fungi and extracellular bacteria. Human T cells producing IL-17 were described as early as the late 1990s in the context of chronic inflammatory conditions small molecule library screening such as rheumatoid arthritis and airway inflammation [1, 2], but it was only in 2005 that they were recognized as a
age of effector T cells [3]. Three lines of evidence obtained in the mouse system supported this notion. First, pathogenic inflammatory T cells produced high levels of IL-17A, IL-17F, and TNF and were dependent on
IL-23 rather than IL-12 for their expansion [3]. Second, naïve CD4+ T cells acquired IL-17-, but not IFN-γ- or IL-4-producing capacity, when activated in vitro in the presence of TGF-β and IL-6 or IL-23 [4-6]. Third, overexpression of the orphan nuclear receptor RORγt was sufficient to Obeticholic Acid in vivo induce differentiation of Th17 cells, while deficiency of RORγt in T cells attenuated autoimmune disease due to lack of tissue-infiltrating Th17 cells [7]. From these groundbreaking studies, the field has progressed at an astonishing pace, taking advantage of new and powerful technologies that have become accessible in recent years. As in many other areas of immunology, discoveries from studies performed in both experimental animal models and in human systems have contributed to our current understanding of the Th17 system and the role these cells play in physiology and pathology. Here, we will review, in particular, studies that address the heterogeneity of human Th17 cells, their differentiation requirements, their migratory capacities, and their role in defense against pathogens. To perform their function, effector, and memory T cells have to migrate to specific tissue sites, which are marked by the presence of constitutive or inflammatory chemokines [8].