Journal
CYTOKINE
Volume 101, Issue -, Pages 4-13Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.cyto.2016.09.001
Keywords
TNF alpha; Th17 cells; Regulatory T cells; Anti-TNF; Interleukin-17
Funding
- Pfizer, UK [WS872934]
- MRC [G0802513] Funding Source: UKRI
Ask authors/readers for more resources
TNF alpha is a principal pro-inflammatory cytokine vital for immunity to infections. However, its excessive production is involved in chronic inflammation and disease pathology in autoimmune diseases. Evidence for its pathogenic role is validated by the fact that its neutralisation by therapeutic agents in vivo is beneficial in ameliorating disease and controlling symptoms. Paradoxically, however, treatment with TNF alpha inhibitors can either have no clinical effects, or even exacerbate disease in some patients. The explanation for such contradictory outcomes may lay in how and which downstream signalling pathways are activated and drive disease. TNF alpha causes its effects by binding to either or both of two membrane-bound receptors, TNFR1 and TNFR2. Engagement of the receptors can induce cell death or cell proliferation. T cells both produce and respond to TNF alpha and depending on whether the cytokine is membrane-bound or soluble and the level of expression of its two receptors, the biological outcome can be distinct. In addition, polymorphisms in genes encoding TNF alpha and T cell signalling proteins can significantly impact the outcome of TNF alpha receptor engagement. Early studies revealed that effector T cells in patients with rheumatoid arthritis (RA) are hyporesponsive due to chronic exposure to TNF alpha. However, recent evidence indicates that the relationship between TNF alpha and T cell responses is complex and, at times, can be paradoxical. In addition, there is controversy as to the specific effects of TNF alpha on different T cell subsets. This review will summarise knowledge on how TNF alpha modulates T cell responses and the effect of engaging either of its two receptors. Furthermore, we discuss how such interactions can dictate the outcome of treatment with TNF alpha inhibitors. (C) 2016 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available