Granulocyte and monocyte apheresis can control juvenile generalized pustular psoriasis with mutation of<i>IL36RN</i>

Koike, Yuta; Okubo, Mitsuo; Kiyohara, Tatsuo; Fukuchi, Reika; Sato, Yukie; Kuwatsuka, Sayaka; Takeichi, Takuya; Akiyama, Masashi; Sugiura, Kazumitsu

doi:10.1111/bjd.15509

Cited by 20 publications

(13 citation statements)

References 15 publications

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“…Clinical case reports also support our findings and the idea of a potential IL-36-macrophage pathway within psoriasis pathology. Two case reports show patients with DITRA, who suffer from a lack of function mutation in the endogenous IL-36RA, benefit from monocyte apheresis treatment ( 44 , 58 ).…”

Section: Discussionmentioning

confidence: 99%

“…The ability of IL-36γ to induce such inflammatory mediators from infiltrating macrophages could escalate the inflammatory cascade by activating surrounding fibroblasts, endothelial cells ( 18 ), and keratinocytes and ultimately lead to further immune cell recruitment. In recent studies, GPP patients with DITRA (Deficiency of IL-36R Antagonist) showed significant disease improvement after receiving monocyte apheresis therapy, highlighting the potential importance of an IL-36-macrophage axis in the pathology of psoriasis ( 43 , 44 ).…”

Section: Introductionmentioning

confidence: 99%

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IL-36γ Is a Strong Inducer of IL-23 in Psoriatic Cells and Activates Angiogenesis

et al. 2018

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The IL-1 family member cytokine IL-36γ is recognised as key mediator in the immunopathology of psoriasis, hallmarks of which involve the activation of both resident and infiltrating inflammatory myeloid cells and aberrant angiogenesis. This research demonstrates a role for IL-36γ in both myeloid activation and angiogenesis. We show that IL-36γ induces the production of psoriasis-associated cytokines from macrophages (IL-23 and TNFα) and that this response is enhanced in macrophages from psoriasis patients. This effect is specific for IL-36γ and could not be mimicked by other IL-1 family cytokines such as IL-1α. IL-36γ was also demonstrated to induce endothelial tube formation and branching, in a VEGF-A-dependent manner. Furthermore, IL-36γ-stimulated macrophages potently activated endothelial cells and led to increased adherence of monocytes, effects that were markedly more pronounced for psoriatic macrophages. Interestingly, regardless of stimulus, psoriasis monocytes showed increased adherence to both the stimulated and unstimulated endothelium when compared with monocytes from healthy individuals. Collectively, these findings show that IL-36γ has the potential to enhance endothelium directed leucocyte infiltration into the skin and strengthen the IL-23/IL-17 pathway adding to the growing evidence of pathogenetic roles for IL-36γ in psoriatic responses. Our findings also point to a cellular response, which could potentially explain cardiovascular comorbidities in psoriasis in the form of endothelial activation and increased monocyte adherence.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

IL-36γ Is a Strong Inducer of IL-23 in Psoriatic Cells and Activates Angiogenesis

et al. 2018

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“…In addition, a transcriptome analysis to profile the gene expression of peripheral blood mononuclear cells from patients with GPP indicates that dysregulated gene expression in peripheral blood may significantly contribute to psoriatic inflammation in patients with GPP (8). In several clinical trials, selective depletion of elevated granulocytes and monocytes by adsorptive apheresis is proved to alleviate GPP symptoms and related disorders (9)(10)(11). It was recently reported that the gene profiling of GPP lesions is enriched in biologic categories including positive regulation of chemotaxis and antimicrobial response, which is in accordance with the characteristics of massive neutrophil infiltration (12).…”

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confidence: 99%

Neutrophil exosomes enhance the skin autoinflammation in generalized pustular psoriasis via activating keratinocytes

et al. 2019

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Generalized pustular psoriasis (GPP) is a rare and severe inflammatory skin disease that can be life‐threatening. Gene mutations are found in some cases, but its immune pathogenesis is largely unknown. Here, we observed that the neutrophil:lymphocyte ratio in patients with GPP was higher than that in healthy controls and decreased after effective treatment. Neutrophils isolated from patients with GPP induced higher expressions of inflammatory genes including IL‐1β, IL‐36G, IL‐18, TNF‐α, and C‐X‐C motif chemokine ligands in keratinocytes than normal neutrophils did. Moreover, neutrophils from patients with GPP secreted more exosomes than controls, which were then rapidly internalized by keratinocytes, increasing the expression of these inflammatory molecules via activating NF‐κB and MAPK signaling pathways. The proteomic profiles in neutrophil exosomes further characterized functional proteins and identified olfactomedin 4 as the critical differentially expressed protein that mediates the autoimmune inflammatory responses of GPP. These results demonstrate that neutrophil exosomes have an immune‐regulatory effect on keratinocytes, which modulates immune cell migration and autoinflammation in GPP.—Shao, S., Fang, H., Zhang, J., Jiang, M., Xue, K., Ma, J., Zhang, J., Lei, J., Zhang, Y., Li, B., Yuan, X., Dang, E., Wang, G. Neutrophil exosomes enhance the skin autoinflammation in generalized pustular psoriasis via activating keratinocytes. FASEB J. 33, 6813–6828 (2019). http://www.fasebj.org

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“…In addition to inducing IL‐23 from myeloid cells, IL‐36 also promotes T‐cell proliferation . Like PsA patients, DITRA patients also benefit from monocyte apheresis treatment . IL‐36 has also been shown to play a role in the imiquimod mouse model of psoriasis, with IL‐36 KO mouse displaying diminished pathology and an absence of epidermal neutrophil infiltration .…”

Section: The Concept Of Il‐23–independent Il‐17 Productionmentioning

confidence: 99%

“…155 Like PsA patients, DITRA patients also benefit from monocyte apheresis treatment. 163,164 IL-36 has also been shown to play a role in the imiquimod mouse model of psoriasis, with IL-36 KO mouse displaying diminished pathology and an absence of epidermal neutrophil infiltration. 165,166 Moreover, when imiquimod model mice are subject to treadmill running experiments, these mice developed inflammation of the enthesis, characterized by infiltrating immune cells.…”

Section: Role Of Il-36 At the Enthesismentioning

confidence: 99%

Interleukin‐23 pathway at the enthesis: The emerging story of enthesitis in spondyloarthropathy

Bridgewood

Sharif

Sherlock

et al. 2020

Immunological Reviews

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The inflammatory disorders collectively termed the seronegative spondyloarthropathies (SpA) include ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, the arthritis associated with inflammatory bowel disease including Crohn's disease and ulcerative colitis, the arthritis related to anterior uveitis, and finally, somewhat controversially Behcet's disease. All of these diseases are associated with SNPs in the IL‐23R or the interleukin‐23 (IL‐23) cytokine itself and related downstream signaling JAK pathway genes and the interleukin‐17 (IL‐17) pathway. In rheumatoid arthritis, the target of the immune response is the synovium but the SpA disorders target the tendon, ligament, and joint capsule skeletal anchorage points that are termed entheses. The discovery that IL‐23R–expressing cells were ensconced in healthy murine enthesis, and other extraskeletal anchorage points including the aortic root and the ciliary body of the eye and that systemic overexpression of IL‐23 resulted in a severe experimental SpA, confirmed a fundamentally different immunobiology to rheumatoid arthritis. Recently, IL‐23R–expressing myeloid cells and various innate and adaptive T cells that produce IL‐17 family cytokines have also been described in the human enthesis. Blockade of IL‐23 pathway with either anti‐p40 or anti‐p19 subunits has resulted in some spectacular therapeutic successes in psoriasis and PsA including improvement in enthesitis in the peripheral skeleton but has failed to demonstrate efficacy in AS that is largely a spinal polyenthesitis. Herein, we discuss the known biology of IL‐23 at the human enthesis and highlight the remarkable emerging story of this unique skeletal tissue.

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Granulocyte and monocyte apheresis can control juvenile generalized pustular psoriasis with mutation ofIL36RN

Cited by 20 publications

References 15 publications

IL-36γ Is a Strong Inducer of IL-23 in Psoriatic Cells and Activates Angiogenesis

IL-36γ Is a Strong Inducer of IL-23 in Psoriatic Cells and Activates Angiogenesis

Neutrophil exosomes enhance the skin autoinflammation in generalized pustular psoriasis via activating keratinocytes

Interleukin‐23 pathway at the enthesis: The emerging story of enthesitis in spondyloarthropathy

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