Abstract
T cells are known to be plastic and to change their phenotype according to the cellular and biochemical milieu they are embedded in. In this study, we transposed this concept at a macroscopic level assessing whether changes in the environmental housing conditions of C57/BL6 mice would influence the phenotype and function of T cells. Our study shows that exposure to 2 weeks in an enriched environment (EE) does not impact the T cell repertoire in vivo and causes no changes in the early TCR-driven activation events of these cells. Surprisingly, however, T cells from enriched mice showed a unique T helper effector cell phenotype upon differentiation in vitro. This was featured by a significant reduction in their ability to produce IFN-γ and by an increased release of IL-10 and IL-17. Microarray analysis of these cells also revealed a unique gene fingerprint with key signaling pathways involved in autoimmunity being modulated. Together, our results provide first evidence for a specific effect of EE on T cell differentiation and its associated changes in gene expression profile. In addition, our study sheds new light on the possible mechanisms by which changes in environmental factors can significantly influence the immune response of the host and favor the resolution of the inflammatory response.
Highlights
Over the past decade, a growing body of research has identified that many immune cells are able to dynamically alter their form and function in response to changes in the local microenvironment
Our results show that a period as short as 2 weeks of housing in an EE causes significant changes to the gene expression profile of T cells as well as their effector function, shifting their profiles from a classical Th1 phenotype toward a more intermediate state featured by a reduction in IFN-γ and an increase in IL-10 and IL-17 production
We first tested the possible effects of EE on the overall T cell repertoire in vivo looking at the CD3, CD4, or CD8 profile in the thymus and lymph nodes
Summary
A growing body of research has identified that many immune cells are able to dynamically alter their form and function in response to changes in the local microenvironment. In the context of the adaptive immune response, an ever-growing number of studies have investigated the experimental conditions (such as skewing cytokines, antigen-presenting cells, or receptor co-stimulation) that favor the differentiation of T cells into a specific effector T helper (Th) type One such example is the multitude of in vitro and in vivo studies on Th17 cells, a differentiated and apparently fully committed Th cell phenotype, which has been shown to switch between a pathogenic, inflammatory and protective, regulatory functions (and vice versa) in accordance with the conditions in which they are cultured [8,9,10,11]. This is surprising considering that a Immunomodulatory Effect of Enriched Environment great deal of literature suggests that after genetics, factors such as pollution [14,15,16], geographical location [17, 18], psychological state [19,20,21,22], and social status [23,24,25,26] are each key determinants in the etiology of autoimmune disorders
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