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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 CD4+CD25+Foxp3+ 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.

SUBMITTER: Nelson A

PROVIDER: S-EPMC6281785 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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

Nelson Alexander A Cunha Christina C Nishimura Michael I MI Iwashima Makio M

Cytokine 20180606

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 CD4+CD25+Foxp3+ regulatory T cells (Tregs) express membrane-bound TNF, a potent activator of the type 2 TNF receptor. Whi ...[more]

PMID: 29885993

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