TNF: Immunosuppressive Actions via Tregs

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  2. TNF: Immunosuppressive Actions via Tregs

Although counter-intuitive, there is increasing evidence that the pro-inflammatory cytokine TNF can activate immunosuppressive Tregs through TNFR2. Hamano et al. further investigate the effects of TNF on Tregs. The authors demonstrate that TNF preferentially upregulates expression of the co-stimulatory TNF receptor superfamily members TNFR2, 4-1BB and OX40 on Tregs, leading to the proliferation of highly suppressive Tregs. These findings are confirmed in vivo, with the administration of neutralizing anti-TNF Ab blocking both the LPS-induced expansion of splenic Tregs and the up-regulation of TNFR2, OX40 and 4-1BB on those cells in mice. These findings suggest that TNF, OX40L and 4-1BBL, which are known inducers of effector T-cell proinflammatory actions, can also activate Tregs and thereby serve in the dampening of the inflammatory response. Hamano et al. Eur J Immunol 2011; 41:2010–2020.