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Front Immunol. 2018 Nov 9;9:2572. doi: 10.3389/fimmu.2018.02572. eCollection 2018.

The Key Role of TNF-TNFR2 Interactions in the Modulation of Allergic Inflammation: A Review.

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Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.
Department of Immunology and Pathology, Monash University, Melbourne, VIC, Australia.
School of Chemical Engineering, Universiti Sains Malaysia, Pulau Pinang, Malaysia.
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, China.
School of Health and Biomedical Sciences, RMIT, Melbourne, VIC, Australia.
Hospital Universiti Sains Malaysia, Universiti Sains Malaysia, Kelantan, Malaysia.


Tumor necrosis factor-alpha (TNF) is a pleiotropic cytokine, which is thought to play a major role in the pathogenesis of inflammatory diseases, including allergy. TNF is produced at the early stage of allergen sensitization, and then continues to promote the inflammation cascade in the effector phase of allergic reactions. Consequently, anti-TNF treatment has been proposed as a potential therapeutic option. However, recent studies reveal anti-intuitive effects of TNF in the activation and proliferative expansion of immunosuppressive Tregs, tolerogenic DCs and MDSCs. This immunosuppressive effect of TNF is mediated by TNFR2, which is preferentially expressed by immunosuppressive cells. These findings redefine the role of TNF in allergic reaction, and suggest that targeting TNF-TNFR2 interaction itself may represent a novel strategy in the treatment of allergy.


TNF; TNFR2; allergy; regulatory T cells; tolerogenic dendritic cells

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