Therapeutic treatment with Ibrutinib attenuates imiquimod-induced psoriasis-like inflammation in mice through downregulation of oxidative and inflammatory mediators in neutrophils and dendritic cells

Al-Harbi, Naif O.; Nadeem, Ahmed; Ahmad, Sheikh F.; Bakheet, Saleh A.; El-Sherbeeny, Ahmed M.; Ibrahim, Khalid E.; Alzahrani, Khalid S.; Alharbi, Mohammed; Mahmood, Hafiz Majid; Alqahtani, Faleh; Attia, Sabry M.; Alotaibi, Moureq R.

doi:10.1016/j.ejphar.2020.173088

Cited by 53 publications

(46 citation statements)

References 58 publications

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“…Hereby, TLRactivated myeloid cells produce cytokines critical for differentiation of IL-17 and IL-22-producing T cells. The finding that BTKi attenuated TLR7-driven psoriasis-like inflammation in mice, most likely by acting on innate immune cells (Al-Harbi et al, 2020;Nadeem et al, 2020), points to BTKi as a promising therapeutic option.…”

Section: Btk and Btki Beyond The B Cell Compartment Psoriasismentioning

confidence: 99%

Targeting Bruton’s Tyrosine Kinase in Inflammatory and Autoimmune Pathologies

Neys

Hendriks

Corneth

2021

Front. Cell Dev. Biol.

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Bruton’s tyrosine kinase (BTK) was discovered due to its importance in B cell development, and it has a critical role in signal transduction downstream of the B cell receptor (BCR). Targeting of BTK with small molecule inhibitors has proven to be efficacious in several B cell malignancies. Interestingly, recent studies reveal increased BTK protein expression in circulating resting B cells of patients with systemic autoimmune disease (AID) compared with healthy controls. Moreover, BTK phosphorylation following BCR stimulation in vitro was enhanced. In addition to its role in BCR signaling, BTK is involved in many other pathways, including pattern recognition, Fc, and chemokine receptor signaling in B cells and myeloid cells. This broad involvement in several immunological pathways provides a rationale for the targeting of BTK in the context of inflammatory and systemic AID. Accordingly, numerous in vitro and in vivo preclinical studies support the potential of BTK targeting in these conditions. Efficacy of BTK inhibitors in various inflammatory and AID has been demonstrated or is currently evaluated in clinical trials. In addition, very recent reports suggest that BTK inhibition may be effective as immunosuppressive therapy to diminish pulmonary hyperinflammation in coronavirus disease 2019 (COVID-19). Here, we review BTK’s function in key signaling pathways in B cells and myeloid cells. Further, we discuss recent advances in targeting BTK in inflammatory and autoimmune pathologies.

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Section: Btk and Btki Beyond The B Cell Compartment Psoriasismentioning

confidence: 99%

Targeting Bruton’s Tyrosine Kinase in Inflammatory and Autoimmune Pathologies

Neys

Hendriks

Corneth

2021

Front. Cell Dev. Biol.

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“…The inflammation that occurs in Ps is associated with skin cells (keratinocytes and fibroblasts) and immune cells (both innate and adaptive) [ 24 ]. Interestingly, the intensity of ROS in the skin is definitely higher than in other tissues [ 25 ].…”

Section: Oxidative Stress and Reactive Oxidative Species In Psoriamentioning

confidence: 99%

“…Dendritic cells and neutrophils are important in the formation of psoriatic lesions, especially in the early stages of the disease [ 24 ]. In addition, they are responsible for the formation of inflammatory infiltrates and microabscesses, characteristic of this type of skin dermatosis [ 86 , 87 ].…”

Section: Perspective Markers Of Oxidative Stress In Psmentioning

confidence: 99%

“…In addition, they are responsible for the formation of inflammatory infiltrates and microabscesses, characteristic of this type of skin dermatosis [ 86 , 87 ]. They also release oxidative mediators that increase inflammation in Ps [ 24 ]. Al-Hrabi et al indicated an increase in the level of oxidative stress in neutrophils and CD11c + DC cells and concurrently, BT kinase (Burton’s tyrosine kinase) increased.…”

Section: Perspective Markers Of Oxidative Stress In Psmentioning

confidence: 99%

“…Al-Hrabi et al indicated an increase in the level of oxidative stress in neutrophils and CD11c + DC cells and concurrently, BT kinase (Burton’s tyrosine kinase) increased. They point to the possibility of using BTK as a therapeutic target in psoriasis because the use of a BTK inhibitor (Ibrutinib) allows a reduction in the level of oxidative stress [ 24 ]. Neutrophils secrete oxidants that have an effect on maintaining inflammation in psoriasis [ 88 ].…”

Section: Perspective Markers Of Oxidative Stress In Psmentioning

confidence: 99%

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Oxidative Stress as an Important Contributor to the Pathogenesis of Psoriasis

Pleńkowska

Gabig-Cimińska

Mozolewski

2020

IJMS

123

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This review discusses how oxidative stress (OS), an imbalance between oxidants and antioxidants in favor of the oxidants, increased production of reactive oxygen species (ROS)/reactive nitrogen species (RNS), and decreased concentration/activity of antioxidants affect the pathogenesis or cause the enhancement of psoriasis (Ps). Here, we also consider how ROS/RNS-induced stress modulates the activity of transcriptional factors and regulates numerous protein kinase cascades that participate in the regulation of crosstalk between autophagy, apoptosis, and regeneration. Answers to these questions will likely uncover novel strategies for the treatment of Ps. Action in the field will avoid destructive effects of ROS/RNS-mediated OS resulting in cellular dysfunction and cell death. The combination of the fragmentary information on the role of OS can provide evidence to extend the full picture of Ps.

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HMGB1 regulates Th17 cell differentiation and function in patients with psoriasis

Zhu,

Dou,

Lin

et al. 2024

Immunity Inflam & Disease

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BackgroundPsoriasis is an immune‐mediated chronic inflammatory skin disease, in which T helper 17 (Th17) cells and its effective cytokine interleukin (IL)‐17A play a pivotal pathogenic role. High mobility group box 1 (HMGB1) is an important proinflammatory cytokine, which has been confirmed to be highly expressed in the peripheral circulation and epidermis tissues of psoriasis patients. The regulatory effect of HMGB1 on IL‐17A expression and function has been reported in some inflammatory and autoimmune diseases by the HMGB1‐Toll‐like receptor 4 (TLR4)‐interleukin (IL)‐23‐IL‐17A pathway. While, in the pathological environment of psoriasis, whether HMGB1 can exert the regulatory effect on IL‐17A is not clear.ObjectiveWe aimed to evaluate the role of HMGB1‐TLR4‐IL‐23‐IL‐17A pathway in the pathogenesis of psoriasis and explore the possible regulatory mechanism of HMGB1 on Th17 cell differentiation.MethodsSerum levels of HMGB1, TLR4, IL‐23, and IL‐17A were quantified in 50 patients with moderate‐to‐severe plaque psoriasis and 30 healthy controls. Peripheral blood mononuclear cells were acquired from 10 severe psoriasis patients and administrated by different concentrations of recombinant‐HMGB1 (rHMGB1) to detect the Th17 cell percentage, mRNA and protein levels of TLR4, IL‐23, IL‐17A and retinoid‐related orphan receptor γt (RORγt).ResultsThe serum levels of HMGB1, TLR4, IL‐23, and IL‐17A in psoriasis patients were significantly higher than healthy controls, especially in severe patients, and positively correlated with the severity index. There were also positive correlations between every two detected indicators of HMGB1, TLR4, IL‐23, and IL‐17A. In vitro study, rHMGB1 can promote the elevated expression of Th17 cell percentage as well as TLR4, IL‐23, IL‐17A, and RORγt in a dose‐dependent manner.ConclusionHMGB1 can contribute to the pathogenesis of psoriasis by regulating Th17 cell differentiation through HMGB1‐TLR4‐IL‐23‐RORγt pathway, then promotes IL‐17A production and aggravates inflammation process. Targeting HMGB1 may be a possible potential candidate for the immunotherapy of psoriasis.

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Therapeutic treatment with Ibrutinib attenuates imiquimod-induced psoriasis-like inflammation in mice through downregulation of oxidative and inflammatory mediators in neutrophils and dendritic cells

Cited by 53 publications

References 58 publications

Targeting Bruton’s Tyrosine Kinase in Inflammatory and Autoimmune Pathologies

Targeting Bruton’s Tyrosine Kinase in Inflammatory and Autoimmune Pathologies

Oxidative Stress as an Important Contributor to the Pathogenesis of Psoriasis

HMGB1 regulates Th17 cell differentiation and function in patients with psoriasis

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