A Targetable, Noncanonical Signal Transducer and Activator of Transcription 3 Activation Induced by the Y-Less Region of IL-22 Receptor Orchestrates Imiquimod-Induced Psoriasis-Like Dermatitis in Mice

Michiels, Camille; Puigdevall, Léna; Cochez, Perrine; Achouri, Younès; Chéou, Paméla; Hendrickx, Emilie; Dauguet, Nicolas; Blanchetot, Christophe; Dumoutier, Laure

doi:10.1016/j.jid.2021.04.016

Cited by 9 publications

(10 citation statements)

References 33 publications

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“… 28 A previous study has indicated that STAT3 is a representative transcription factor known to that play a critical role in inflammation-associated diseases through multi-level participation. 29 Moreover, inflammation is a crucial factor mediating high UA levels as well as CAS. 30 Chronic inflammation can accelerate the process of aging.…”

Section: Discussionmentioning

confidence: 99%

High Level of Serum Uric Acid induced Monocyte Inflammation is Related to Coronary Calcium Deposition in the Middle-Aged and Elder Population of China: A five-year Prospective Cohort Study

Wang¹,

Liu²,

Qi³

et al. 2022

JIR

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Background Serum uric acid (SUA) is suspected to be associated with atherosclerosis and calcium deposition in atherosclerosis is known to related poor prognosis, yet there is no cohort study on the aged in China. We aimed to investigate the relationships between SUA levels and coronary calcium deposition in the middle-aged and elderly populations in China. Methods A total of 326 participants between the ages of 50 and 85 who had undergone a coronary CT scan in 2015 at the Huadong Hospital Affiliated to Fudan University (Shanghai, China) were included in this study. Univariate and multivariate binary logistic regression was performed to analyze the correlation between SUA levels and coronary artery calcium score (CACS). The changes in CACS during a five-year follow-up were analyzed through Kaplan–Meier survival and binary cox regression analysis. An observational study was done on another 104 asymptomatic middle-aged and elderly patients to compare relative mRNA expressions of proinflammatory factors in peripheral blood mononuclear cells (PBMCs) from 104 subjects. Results Based on the first year of follow-up data analysis, the elevation of SUA levels ( P <0.001) is an independent risk factor for the increase of CACS after coordinating the confounding factors. According to five-year follow-up data, cox regression analysis proved that SUA was a risk factor for CACS (HR =5.86, P <0.001). The mRNA expression of IL-6 and CXCL8 in the HUA and HUA patients with CAC (HUA-CAC) groups was significantly higher than that in the normal control (NC) and coronary calcium deposition (CAC) groups. Conclusion Taken together, the findings in this study indicate that high SUA levels ( P <0.001) are an independent risk factor for CACS and elevated SUA levels increase the risk of developing coronary calcium deposition among middle-aged and old people in the Chinese population, which may be related to an increase of pro-inflammatory cytokines in the PBMCs.

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Section: Discussionmentioning

confidence: 99%

High Level of Serum Uric Acid induced Monocyte Inflammation is Related to Coronary Calcium Deposition in the Middle-Aged and Elder Population of China: A five-year Prospective Cohort Study

Wang¹,

Liu²,

Qi³

et al. 2022

JIR

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“…IL-22 signaling is crucial in the early phase of host defense against intestinal infection. In contrast to WT mice, Il22 −/− and Il22r −/− mice are highly susceptible to C. rodentium infection, which causes severe epithelial damage in the intestine, weight loss, systemic bacterial burden, and high mortality in these mice [ 19 , 27 ]. We thus tested whether TGF-β1 blockade with anti-GARP:TGF-β1 mAbs would increase the severity of disease in these mice.…”

Section: Resultsmentioning

confidence: 99%

Blocking GARP-mediated activation of TGF-β1 did not alter innate or adaptive immune responses to bacterial infection or protein immunization in mice

Gaignage

Zhang

Stockis

et al. 2022

Cancer Immunol Immunother

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Transmembrane protein GARP binds latent TGF-β1 to form GARP:(latent)TGF-β1 complexes on the surface of several cell types including Tregs, B-cells, and platelets. Upon stimulation, these cells release active TGF-β1. Blocking TGF-β1 activation by Tregs with anti-GARP:TGF-β1 mAbs overcomes resistance to PD1/PD-L1 blockade and induces immune-mediated regressions of murine tumors, indicating that Treg-derived TGF-β1 inhibits anti-tumor immunity. TGF-β1 exerts a vast array of effects on immune responses. For example, it favors differentiation of TH17 cells and B-cell switch to IgA production, two important processes for mucosal immunity. Here, we sought to determine whether treatment with anti-GARP:TGF-β1 mAbs would perturb immune responses to intestinal bacterial infection. We observed no aggravation of intestinal disease, no systemic dissemination, and no alteration of innate or adaptative immune responses upon oral gavage of C. rodentium in highly susceptible Il22r−/− mice treated with anti-GARP:TGF-β1 mAbs. To examine the effects of GARP:TGF-β1 blockade on Ig production, we compared B cell- and TH cell- responses to OVA or CTB protein immunization in mice carrying deletions of Garp in Tregs, B cells, or platelets. No alteration of adaptive immune responses to protein immunization was observed in the absence of GARP on any of these cells. Altogether, we show that antibody-mediated blockade of GARP:TGF-β1 or genetic deletion of Garp in Tregs, B cells or platelets, do not alter innate or adaptive immune responses to intestinal bacterial infection or protein immunization in mice. Anti-GARP:TGF-β1 mAbs, currently tested for cancer immunotherapy, may thus restore anti-tumor immunity without severely impairing other immune defenses. Précis Immunotherapy with GARP:TGF-β1 mAbs may restore anti-tumor immunity without impairing immune or inflammatory responses required to maintain homeostasis or host defense against infection, notably at mucosal barriers.

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“…In addition, in a psoriasis‐like dermatitis model induced by imiquimod in which IL‐22 and STAT3 are known to be deleterious, mice expressing a C‐terminally truncated version of IL‐22Rα (ΔCter mut/mut mice) are protected from the development of skin lesions, demonstrating the importance of the noncanonical STAT3 pathway. In this model, ΔCter mut/mut mice show less thickening of ear epidermis as compared to WT littermate mice 10 …”

Section: Receptor‐phosphotyrosine‐independent Mechanismsmentioning

confidence: 96%

“…In this model, ΔCter mut/mut mice show less thickening of ear epidermis as compared to WT littermate mice. 10 F I G U R E 2 Receptors that signal through a phosphotyrosine-independent pathway. (A) hIL-22R, (B) hIFNλ-R, (C) mIL-23R, (D) hG-CSFR and (E) hIFNAR signal through a classical JAK-STAT signalling pathway as well as an alternative pathway.…”

Section: Il-22rαmentioning

confidence: 99%

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JAK/STAT: Why choose a classical or an alternative pathway when you can have both?

Puigdevall

Michiels

Stewardson

et al. 2022

J Cellular Molecular Medi

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Processes such as cellular proliferation, differentiation, growth and apoptosis are regulated in part by numerous extracellular factors including cytokines. These glycoproteins, which have an immunomodulatory role, are also mainly secreted by cells of the immune system. They perform their paracrine, juxtacrine, autocrine or endocrine actions by binding to specific cytokine receptors at the cell surface. A subset of cytokines triggers the JAK/STAT pathway to exert biological functions 1,2 (Figure 1). Their receptors are homodimers or hetero-dimers/trimers of transmembrane proteins that lack intracellular kinase activity. Instead, they rely on constitutive association with intracellular tyrosine kinases called Janus kinases (JAK) for the transduction of cytokine signalling.The Janus kinase family consists of four members: JAK1, JAK2, JAK3 and TYK2 that are ubiquitously expressed, except for JAK3 whose expression is restricted to cells of the haematopoietic lineage. JAKs, which are associated with the juxta-membrane domain of the receptor, become active when cytokine binds the receptor. Following this binding, the receptor undergoes intracellular conformational changes that result in its re-orientation or oligomerization. This initiates the signalling process by juxtaposing

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A Targetable, Noncanonical Signal Transducer and Activator of Transcription 3 Activation Induced by the Y-Less Region of IL-22 Receptor Orchestrates Imiquimod-Induced Psoriasis-Like Dermatitis in Mice

Cited by 9 publications

References 33 publications

High Level of Serum Uric Acid induced Monocyte Inflammation is Related to Coronary Calcium Deposition in the Middle-Aged and Elder Population of China: A five-year Prospective Cohort Study

High Level of Serum Uric Acid induced Monocyte Inflammation is Related to Coronary Calcium Deposition in the Middle-Aged and Elder Population of China: A five-year Prospective Cohort Study

Blocking GARP-mediated activation of TGF-β1 did not alter innate or adaptive immune responses to bacterial infection or protein immunization in mice

JAK/STAT: Why choose a classical or an alternative pathway when you can have both?

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