Pigmented Necrobiosis Lipoidica Accompanied by Insulin-dependent Diabetes Mellitus Induces CD163 Proinflammatory Macrophages and Interleukin-17-producing Cells

Wakusawa, Chihiro; Fujimura, Taku; Kambayashi, Yahiko; Furudate, Sadanori; Hashimoto, Akira; Aiba, Setsuya

doi:10.2340/00015555-1502

Cited by 10 publications

(7 citation statements)

References 13 publications

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“…Consistent with this is the demonstration that CD163-positive macrophages infiltrating the fibrous tissue in facet joints of patients with ankylosing spondylitis are a major source of inflammatory cytokines, such IL-23 [35]. Wakusawa et al described a patient with Necrobiosis lipoidica associated with Insulin-dependent type 1 diabetes mellitus, in which granulomas contained mostly pro-inflammatory CD163-positive macrophages [36]. Increased expression of CD163 has been also seen in skin macrophages and peripheral blood monocytes of patients with systemic sclerosis, an autoimmune disease characterized by local inflammatory infiltrates and widespread fibrosis [37].…”

Section: Discussionmentioning

confidence: 80%

Lesional Accumulation of CD163-Expressing Cells in the Gut of Patients with Inflammatory Bowel Disease

et al. 2013

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Monocytes/macrophages displaying different markers of activation/differentiation infiltrate the inflamed gut of patients with inflammatory bowel diseases (IBD), but the role that each monocyte/macrophage subpopulation plays in the pathogenesis of IBD is not fully understood. The hemoglobin scavenger receptor CD163, a specific marker of monocytes/macrophages, has been associated with either anti-inflammatory or inflammatory functions of macrophages in several pathologies. In this study we examined the tissue distribution and function of CD163-expressing monocytes/macrophages in IBD. CD163 RNA and protein expression was more pronounced in IBD in comparison to normal controls, with no significant difference between Crohn's disease and Ulcerative colitis. In IBD, over-expression of CD163 was restricted to areas with active inflammation and not influenced by current therapy. Immunohistochemical analysis confirmed the accumulation of CD163-expressing cells in IBD, mostly around and inside blood vessels, thus suggesting that these cells are partly recruited from the systemic circulation. Indeed, FACS analysis of circulating mononuclear cells showed that the fractions of CD163-positive monocytes were increased in IBD patients as compared to controls. Functionally, interleukin-6 up-regulated CD163 expression in lamina propria mononuclear cells and mucosal explants of normal subjects. In IBD blood and mucosal cell cultures, cross-linking of CD163 with a specific monoclonal anti-CD163 antibody enhanced tumor necrosis factor-α synthesis. These findings indicate that IBD mucosa is abundantly infiltrated with CD163-positive cells, which could contribute to amplify the inflammatory cytokine response.

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Section: Discussionmentioning

confidence: 80%

Lesional Accumulation of CD163-Expressing Cells in the Gut of Patients with Inflammatory Bowel Disease

et al. 2013

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“…Moreover, they reported in another study that the Th17:Treg ratio was significantly higher in low-risk MDS compared with highrisk MDS (4). on the other hand, we recently reported the distribution of Foxp3 + Tregs and IL-17-producing cells in several cases of cutaneous granulomatous dermatitis, including sarcoidosis, granuloma annulare, necrobiosis lipoidica, granulomatous pigmented and purpuric dermatitis (8)(9)(10). on the other hand, we recently reported the distribution of Foxp3 + Tregs and IL-17-producing cells in several cases of cutaneous granulomatous dermatitis, including sarcoidosis, granuloma annulare, necrobiosis lipoidica, granulomatous pigmented and purpuric dermatitis (8)(9)(10).…”

Section: Discussionmentioning

confidence: 89%

Generalized Granulomatous Dermatitis Accompanied by Myelodysplastic Syndrome

Hagiwara¹,

Fujimura²,

Furudate³

et al. 2014

Acta Derm Venerol

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“…Secukinumab is a fully human monoclonal antibody that binds IL-17A, preventing it from binding to the receptor for IL-17, consequently inhibiting the action of this pro-inflammatory cytokine [ 84 ]. Wakusawa et al, in sections taken from NL lesions, revealed the presence of granulomas containing significant amounts of IL-17-releasing cells; therefore, this cytokine was associated with NL [ 85 ]. Gibson et al described four clinical cases of patients with treatment-resistant NL who received subcutaneous secukinumab for 24 weeks [ 78 ].…”

Section: Treatment Standards and New Therapeutic Optionsmentioning

confidence: 99%

A Breakthrough in the Treatment of Necrobiosis Lipoidica? Update on Treatment, Etiopathogenesis, Diagnosis, and Clinical Presentation

Naumowicz,

Modzelewski,

Macko

et al. 2024

IJMS

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Necrobiosis lipoidica (NL) is a rare granulomatous disease of a not fully understood etiopathogenesis. Classically, NL is associated with insulin-dependent diabetes mellitus. The disease often fails to respond to conventional treatments and adversely affects patients’ quality of life. First-line medications are usually topical corticosteroids, but patients respond to them with varying degrees of success. Other options include tacrolimus, phototherapy, cyclosporine, fumaric acid esters, and biologics (adalimumab, etanercept, and infliximab). Our review aims to present new therapeutic approaches potentially effective in patients with refractory lesions, describe the presumed etiopathogenesis, and provide diagnostic guidance for clinicians. The review concludes that Janus kinase inhibitors and biologics such as ustekinumab and secukinumab can be used effectively in patients with recalcitrant NL. Another promising treatment option is tapinarof (an aryl hydrocarbon receptor agonist). However, studies on larger groups of patients are still needed to evaluate the effectiveness of different therapeutic options and to define consistent treatment regimens for NL. It is advisable to improve the awareness of physicians of various specialties regarding necrobiosis lipoidica as lesions diagnosed earlier usually have a better response to treatment.

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Pigmented Necrobiosis Lipoidica Accompanied by Insulin-dependent Diabetes Mellitus Induces CD163 Proinflammatory Macrophages and Interleukin-17-producing Cells

Cited by 10 publications

References 13 publications

Lesional Accumulation of CD163-Expressing Cells in the Gut of Patients with Inflammatory Bowel Disease

Lesional Accumulation of CD163-Expressing Cells in the Gut of Patients with Inflammatory Bowel Disease

Generalized Granulomatous Dermatitis Accompanied by Myelodysplastic Syndrome

A Breakthrough in the Treatment of Necrobiosis Lipoidica? Update on Treatment, Etiopathogenesis, Diagnosis, and Clinical Presentation

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