Beyond TNF: TNF superfamily cytokines as targets for the treatment of rheumatic diseases

Croft, Michael; Siegel, Richard M.

doi:10.1038/nrrheum.2017.22

Cited by 237 publications

(204 citation statements)

References 226 publications

(236 reference statements)

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“…The TNF superfamily (TNFSF) comprises 19 ligands and 29 receptors (TNF superfamily receptors, TNFRSFs), which promotes survival, proliferation, differentiation, and apoptosis in various cells, such as T cells, B cells, and dendritic cells . The majority of TNF superfamily ligands constitute type 2 transmembrane proteins containing a TNF homology domain and are released from the cell membrane by proteolysis to act as cytokines.…”

Section: Co‐stimulatory Cytokines (Il‐2 Il‐4 Il‐7 Il‐9 Tslp Tnfsmentioning

confidence: 99%

The group 2 innate lymphoid cell (ILC2) regulatory network and its underlying mechanisms

Kabata

Moro

Koyasu

2018

Immunological Reviews

229

183

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Summary Group 2 innate lymphoid cells (ILC2s) play critical roles in the induction of type 2 inflammation, response to parasite infection, metabolic homeostasis, and tissue repair. These multifunctional roles of ILC2s are tightly controlled by complex regulatory systems in the local microenvironment, the disruption of which may cause various health problems. This review summarizes up‐to‐date knowledge regarding positive and negative regulators for ILC2s based on their function and signaling pathways, including activating cytokines (IL‐33, IL‐25; MAPK, NF‐κB pathways), co‐stimulatory cytokines (IL‐2, IL‐7, IL‐9, TSLP; STAT5, IL‐4; STAT6, TNF superfamily; MAPK, NF‐κB pathways), suppressive cytokines (type1 IFNs, IFN‐γ, IL‐27; STAT1, IL‐10, TGF‐β), transdifferentiation cytokines (IL‐12; STAT4, IL‐1β, IL‐18), lipid mediators (LTC4, LTD4, LTE4, PGD2; Ca2+‐NFAT pathways, PGE2, PGI2; AC/cAMP/PKA pathways, LXA4, LTB4), neuropeptides (NMU; Ca2+‐NFAT, MAPK pathways, VIP, CGRP, catecholamine, acetylcholine), sex hormones (androgen, estrogen), nutrients (butyrate; HDAC inhibitors, vitamins), and cell‐to‐cell interactions (ICOSL‐ICOS; STAT5, B7‐H6‐NKp30, E‐cadherin‐KLRG1). This comprehensive review affords a better understanding of the regulatory network system for ILC2s, providing impetus to develop new treatment strategies for ILC2‐related health problems.

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Section: Co‐stimulatory Cytokines (Il‐2 Il‐4 Il‐7 Il‐9 Tslp Tnfsmentioning

confidence: 99%

The group 2 innate lymphoid cell (ILC2) regulatory network and its underlying mechanisms

Kabata

Moro

Koyasu

2018

Immunological Reviews

229

183

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“…TNFs are a kind of cytokines produced by activated monocyte-macrophages with multi-functions, such as killing tumor cells, mediating inflammatory response, regulating neuronal activity (e.g., sleep regulation) [25]. The TNF-α and TNF-β, two main numbers of TNF superfamily derived from different-type cells, bind to the common receptors (TNF-R1 and TNF-R2) with similar biological functions.…”

Section: Discussionmentioning

confidence: 99%

The Correlations Between TNF System and Memories in Chronic Insomnia Disorder

Chen

Xia

et al. 2020

J. Adv. Neurosci. Res.

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Objectives: To explore the changes of serum levels of tumor necrosis factors (TNF-α and TNF-β) and their soluble receptors (sTNF-R1 and sTNF-R2), and analyze their relationship between sleep quality and memory in the patients with chronic insomnia disorder (CID).Methods: Forty-four CID patients and 39 normal controls were enrolled in this study. Pittsburgh Sleep Quality Index (PSQI) and Nine-Box Maze Test (9BMT) were used to assess the sleep quality and memory function, respectively. The serum levels of TNF-α, TNF-β, sTNF-R1 and sTNF-R2 were examined by protein-chip.Results: Compared to the controls, the CID patients had significantly higher error numbers of the spatial working and object recognition memories (Ps < 0.05) in the 9BMT, with higher serum levels of TNF-α and TNF-β (Ps < 0.001), and lower levels of sTNF-R1 and sTNF-R2 (Ps < 0.001). The partial correlation analysis showed that the serum TNF-α and TNF-β positively but sTNF-R1 and sTNF-R2 negatively correlated with PSQI scores (Ps < 0.001). In the CID patients, the TNF-α positively correlated with the errors in the spatial working and object recognition memories (Ps < 0.05), whereas the TNF-β only positively correlated with the errors in the spatial working memory (P < 0.05). Conclusions:The CID patients had increased TNF-α and TNF-β and decreased sTNF-R1 and sTNF-R2 in peripheral blood, with the former being linked to specific memory impairments.

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“…Overall, these molecules comprise a structurally related group of ligands, receptors, and inhibitory decoy receptors, with tissue-specific expression, ligand-receptor binding and biological functions [2, 3]. …”

Section: Introductionmentioning

confidence: 99%

Small molecules to the rescue: Inhibition of cytokine signaling in immune-mediated diseases

Gadina

Gazaniga

Vian

et al. 2017

Journal of Autoimmunity

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Cytokines are small, secreted proteins associated with the maintenance of immune homeostasis but also implicated with the pathogenesis of several autoimmune and inflammatory diseases. Biologic agents blocking cytokines or their receptors have revolutionized the treatment of such pathologies. Nonetheless, some patients fail to respond to these drugs or do not achieve complete remission. The signal transduction originating from membrane-bound cytokine receptors is an intricate network of events that lead to gene expression and ultimately regulate cellular functionality. Our understanding of the intracellular actions that molecules such as interleukins, inteferons (IFNs) and tumor necrosis factor (TNF) set into motion has greatly increased in the past few years, making it possible to interfere with cytokines’ signaling cascades. The Janus kinase (JAK)/signal transducer and activator of transcription (STAT), the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), the mitogen activated protein kinase (MAPK) and the Phosphatidylinositol-3’-kinases (PI3K) pathways have all been intensively studied and key steps as well as molecules have been identified. These research efforts have led to the development of a new generation of small molecule inhibitors. Drugs capable of blocking JAK enzymatic activity or interfering with the proteasome-mediated degradation of intermediates in the NF-kB pathway have already entered the clinical arena confirming the validity of this approach. In this review, we have recapitulated the biochemical events downstream of cytokine receptors and discussed some of the drugs which have already been successfully utilized in the clinic. Moreover, we have highlighted some of the new molecules that are currently being developed for the treatment of immune-mediated pathologies and malignancies.

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Beyond TNF: TNF superfamily cytokines as targets for the treatment of rheumatic diseases

Cited by 237 publications

References 226 publications

The group 2 innate lymphoid cell (ILC2) regulatory network and its underlying mechanisms

The group 2 innate lymphoid cell (ILC2) regulatory network and its underlying mechanisms

The Correlations Between TNF System and Memories in Chronic Insomnia Disorder

Small molecules to the rescue: Inhibition of cytokine signaling in immune-mediated diseases

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