Impact of Enriched Environment on Murine T Cell Differentiation and Gene Expression Profile

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.

Environmental stimuli shape microglial plasticity in glioma

“…Anti-tumor activity of an EE has been shown in different cancers ( Cao et al, 2010 ; Nachat-Kappes et al, 2012 ; Garofalo et al, 2015 ), even if some results were not confirmed ( Westwood et al, 2013 ). Environmental stimuli also shape immune functions, modulating NK cells ( Garofalo et al, 2015 ; Song et al, 2017 ), T helper cells ( Rattazzi et al, 2016 ), and myeloid cells ( Chabry et al, 2015 ). NK cells exert anti-tumor function by direct cytotoxic activity, producing several cytokines, chemokines and growth factors ( Vivier et al, 2011 ; Guillerey and Smyth, 2016 ; Stabile et al, 2017 ).…”

Enriched environment regulates thymocyte development and alleviates experimental autoimmune encephalomyelitis in mice

“…A recent publication reports that EE leads to a unique T helper effector cell phenotype upon differentiation in vitro featured by reduced production of IFN-γ although no in vivo impact was observed (37). In contrast, our in vivo data in naïve or EAE conditions demonstrated significant impact of EE on thymocyte differentiation and T cell repertoire.…”

Affective Immunology: The Crosstalk Between Microglia and Astrocytes Plays Key Role?

“…For instance, people with positive emotions showed lower susceptibility to infection ( 15 , 16 ) and greater immune response ( 17 , 18 ). This role of “immune enhancer” is mediated by higher levels of antibodies ( 18 ) and T cells ( 19 – 21 ), and increased activity of natural killer (NK) cells ( 19 , 22 ), as well as reduced inflammatory markers including interleukin-6 (IL-6) and C-reactive protein (CRP) ( 22 , 23 ). In contrast, negative emotions (e.g., sadness, nervousness, worry, loneliness, and fear) and psychological stress are associated with poorer immunological function with lower NK cell cytotoxicity ( 8 ), fewer T cells ( 24 ), and increased inflammatory markers ( 25 ).…”