Activated human Foxp3 regulatory T cells produce membrane-bound TNF. Journal Article

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Authors: Nelson, A; Cunha, C; Nishimura, MI; Iwashima, M
Article Title: Activated human Foxp3 regulatory T cells produce membrane-bound TNF.
Abstract: TNF is a multifunctional cytokine that is critical to host defense against pathogens but can also drive the pathophysiology of inflammatory diseases. Inhibition of TNF occasionally causes exacerbation of some autoimmune diseases, suggesting a role for TNF in the regulation of immune homeostasis. Here, we demonstrate that human peripheral blood CD4CD25Foxp3 regulatory T cells (Tregs) express membrane-bound TNF, a potent activator of the type 2 TNF receptor. While the type 1 TNF receptor can cause cell death and is expressed ubiquitously, the type 2 receptor promotes cell growth and its expression is limited mainly to immune and endothelial cells. When autocrine TNF is blocked in an in vitro culture without IL-2, activated Tregs stop proliferating. These data indicate a novel role for TNF as a Treg-derived autocrine growth factor.
Journal Title: Cytokine
ISSN: 1096-0023; 1043-4666
Publisher: Unknown  
Date Published: 2018