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Review
. 2021 Jul 9:12:686155.
doi: 10.3389/fimmu.2021.686155. eCollection 2021.

Promising Therapeutic Targets for Treatment of Rheumatoid Arthritis

Jie Huang  1 , Xuekun Fu  1 , Xinxin Chen  1 , Zheng Li  1 , Yuhong Huang  1 , Chao Liang  1   2
Affiliations
Review

Promising Therapeutic Targets for Treatment of Rheumatoid Arthritis

Jie Huang et al. Front Immunol. .

Abstract

Rheumatoid arthritis (RA) is a systemic poly-articular chronic autoimmune joint disease that mainly damages the hands and feet, which affects 0.5% to 1.0% of the population worldwide. With the sustained development of disease-modifying antirheumatic drugs (DMARDs), significant success has been achieved for preventing and relieving disease activity in RA patients. Unfortunately, some patients still show limited response to DMARDs, which puts forward new requirements for special targets and novel therapies. Understanding the pathogenetic roles of the various molecules in RA could facilitate discovery of potential therapeutic targets and approaches. In this review, both existing and emerging targets, including the proteins, small molecular metabolites, and epigenetic regulators related to RA, are discussed, with a focus on the mechanisms that result in inflammation and the development of new drugs for blocking the various modulators in RA.

Keywords: epigenetic regulators; proteins; rheumatoid arthritis; small molecular metabolites; targets.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Action of drugs targeting cytokines in rheumatoid arthritis. ADA, adalimumab; CZP, certolizumab; ETN, etanercept; GLM, golimumab; IFX, infliximab; CAK, canakinumab; GEK, gevokizumab; TOC, tocilizumab; SAR, sarilumab; CLZ, clazakizumab; OLK, olokizumab; SIR, sirukumab; OTL, otelixizumab; IXE, ixekizumab; SEC, secukinumab; OTL, otilimab; GIL, gimsilumab; NAL, namilumab; MAL, mavrilimumab; FLS, fibroblast-like synoviocytes; DC, dendritic cell; NK, natural killer cell; TNF-α, tumor necrosis factor-α; IL-1, IL-6, IL-10, IL-15, IL-17, IL-18, interleukin (IL)-1, -6, -10, -15, -17, -17, respectively; IFN-γ, interferon-gamma; GM-CSF, granulocyte-macrophage colony stimulating factor.
Figure 2
Figure 2
Action of drugs targeting chemokines in rheumatoid arthritis. FLS, fibroblast-like synoviocytes; DC, dendritic cell; CXCL1, CXCL2, CXCL5, CXCL8, CXCL10, CXCL12, CXCL13, CXCL16, CXC motif ligand-1, -2, -5, -8, -10, -12, -13, -16; CXCR1/2, CXCR3, CXCR4, CXCR6, CXC motif receptor-1/2, -3, -4, -6; CCL2, CCL3, CCL5, CCL20, CCL25, CC motif ligand -2, -3, -5, -20, -25; CCR1, CCR2, CCR5, CCR9, CC motif receptor-1, -2, -5, -9; CX3CL1, CX3C ligand 1.
Figure 3
Figure 3
Action of drugs targeting small molecular metabolites in rheumatoid arthritis. (A) action of drugs targeting PGs family in rheumatoid arthritis; (B) action of drugs targeting LTs family in rheumatoid arthritis; (C) action of drugs targeting LXs family in rheumatoid arthritis; (D) action of drugs targeting PAF in rheumatoid arthritis. PGD2, prostaglandin D2; PGE2, prostaglandin E2; PGI2, prostaglandin I2; PGJ2, prostaglandin J2; TXA2, thromboxane A2; PGF2α, prostaglandin F2α; DP1, prostaglandin D2 receptor 1; EP4, prostaglandin E receptor 4; TP, prostaglandin TXA2 receptor; FP, prostaglandin PGF2α receptor; IP, prostaglandin PGI2 receptor; LTB4, leukotriene B4; CysLT1, cysteine leukotrienes 1; ALX, lipoxin A4 receptor; FPR-2, formyl peptide receptor-2; PAF, platelet-activating factor; PAFR, platelet-activating factor receptor; iNOS, inducible nitric oxide synthase.
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