Role of regulatory T cells in psoriasis pathogenesis and treatment

Nußbaum, Lea; Chen, Y.L.; Ogg, Graham S.

doi:10.1111/bjd.19380

Cited by 163 publications

(122 citation statements)

References 147 publications

(338 reference statements)

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“… 14 15 p19 and p40 inhibitors may also have differential effects on tissue production of cytokines or on the regulatory effects of Th1/T-helper type 1 cells. 16 It would also be interesting to compare these results with direct inhibition of IL-17, although monoclonal IL-17A antibodies may confound direct measurement of IL-17A levels.…”

Section: Discussionmentioning

confidence: 99%

Guselkumab induces robust reduction in acute phase proteins and type 17 effector cytokines in active psoriatic arthritis: results from phase 3 trials

et al. 2021

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ObjectiveTo investigate serum protein expression in participants with psoriatic arthritis (PsA) and changes after guselkumab treatment.MethodsParticipants with PsA were treated with guselkumab or placebo in the DISCOVER-1 and DISCOVER-2 studies. Serum levels of acute phase reactants C reactive protein (CRP) and serum amyloid A (SAA) and inflammatory cytokines/chemokines were measured at weeks 0, 4 and 24 in 300 study participants and 34 healthy controls (HCs). The PSUMMIT studies measured serum interleukin (IL)-17A, IL-17F and CRP after ustekinumab treatment and levels with ustekinumab versus guselkumab treatment were compared.ResultsBaseline serum levels of CRP, SAA, IL-6, IL-17A and IL-17F were elevated in participants with active PsA vs HCs (p<0.05, geometric mean (GM) ≥40% higher). Baseline T-helper cell 17 (Th17) effector cytokines were significantly associated with baseline psoriasis but not joint disease activity. Compared with placebo, guselkumab treatment resulted in decreases in serum CRP, SAA, IL-6, IL-17A, IL-17F and IL-22 as early as week 4 and continued to decrease through week 24 (p<0.05, GM decrease from baseline ≥33%). At week 24, IL-17A and IL-17F levels were not significantly different from HCs, suggesting normalisation of peripheral IL-23/Th17 axis effector cytokines postguselkumab treatment. Reductions in IL-17A/IL-17F levels were greater in guselkumab-treated versus ustekinumab-treated participants, whereas effects on CRP levels were similar.ConclusionGuselkumab treatment reduced serum protein levels of acute phase and Th17 effector cytokines and achieved comparable levels to those in HCs. In participants with PsA, reductions of IL-17A and IL-17F were of greater magnitude after treatment with guselkumab than with ustekinumab.

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Section: Discussionmentioning

confidence: 99%

Guselkumab induces robust reduction in acute phase proteins and type 17 effector cytokines in active psoriatic arthritis: results from phase 3 trials

et al. 2021

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“…It is proposed that Tregs manipulate and control immune responses using a variety of mechanisms [ 183 , 184 , 185 ]. Absent, reduced or suboptimal Treg responses have been implicated in many human autoimmune diseases including Psoriasis [ 186 , 187 , 188 , 189 ], MS [ 190 , 191 , 192 ], Systemic Sclerosis and Morphoea [ 193 , 194 ], SLE [ 195 ] and RA [ 196 , 197 ]. Additionally, the role of Tregs have been extensively studied in the development of T1D [ 198 , 199 , 200 , 201 , 202 , 203 , 204 ].…”

Section: Regulatory T Cells (Tregs)mentioning

confidence: 99%

The Many Faces of CD4+ T Cells: Immunological and Structural Characteristics

Chatzileontiadou

Sloane

Nguyen

et al. 2020

IJMS

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As a major arm of the cellular immune response, CD4+ T cells are important in the control and clearance of infections. Primarily described as helpers, CD4+ T cells play an integral role in the development and activation of B cells and CD8+ T cells. CD4+ T cells are incredibly heterogeneous, and can be divided into six main lineages based on distinct profiles, namely T helper 1, 2, 17 and 22 (Th1, Th2, Th17, Th22), regulatory T cells (Treg) and T follicular helper cells (Tfh). Recent advances in structural biology have allowed for a detailed characterisation of the molecular mechanisms that drive CD4+ T cell recognition. In this review, we discuss the defining features of the main human CD4+ T cell lineages and their role in immunity, as well as their structural characteristics underlying their detection of pathogens.

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“…IL-6, IL-12, and IL-23; this results in T cell differentiation and activation, forming a positiv feedback loop to drive psoriatic inflammation [66][67][68][69][70].…”

Section: Major Cellular Signal Transduction Pathways Involved In the Development Of Psoriasismentioning

confidence: 99%

Therapeutic Development Based on the Immunopathogenic Mechanisms of Psoriasis

et al. 2021

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Psoriasis, a complex inflammatory autoimmune skin disorder that affects 2–3% of the global population, is thought to be genetically predetermined and induced by environmental and immunological factors. In the past decades, basic and clinical studies have significantly expanded knowledge on the molecular, cellular, and immunological mechanisms underlying the pathogenesis of psoriasis. Based on these pathogenic mechanisms, the current disease model emphasizes the role of aberrant Th1 and Th17 responses. Th1 and Th17 immune responses are regulated by a complex network of different cytokines, including TNF-α, IL-17, and IL-23; signal transduction pathways downstream to the cytokine receptors; and various activated transcription factors, including NF-κB, interferon regulatory factors (IRFs), and signal transducer and activator of transcriptions (STATs). The biologics developed to specifically target the cytokines have achieved a better efficacy and safety for the systemic management of psoriasis compared with traditional treatments. Nevertheless, the current therapeutics can only alleviate the symptoms; there is still no cure for psoriasis. Therefore, the development of more effective, safe, and affordable therapeutics for psoriasis is important. In this review, we discussed the current trend of therapeutic development for psoriasis based on the recent discoveries in the immune modulation of the inflammatory response in psoriasis.

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Role of regulatory T cells in psoriasis pathogenesis and treatment

Cited by 163 publications

References 147 publications

Guselkumab induces robust reduction in acute phase proteins and type 17 effector cytokines in active psoriatic arthritis: results from phase 3 trials

Guselkumab induces robust reduction in acute phase proteins and type 17 effector cytokines in active psoriatic arthritis: results from phase 3 trials

The Many Faces of CD4+ T Cells: Immunological and Structural Characteristics

Therapeutic Development Based on the Immunopathogenic Mechanisms of Psoriasis

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