Co-culture of healthy human keratinocytes and T-cells promotes keratinocyte chemokine production and RORγt-positive IL-17 producing T-cell populations

Peters, Jorieke H.; Tjabringa, Geuranne S.; Fasse, Esther; Oliveira, Victor De; Schalkwijk, Joost; Koenen, Hans J. P. M.; Joosten, Irma

doi:10.1016/j.jdermsci.2012.10.004

Cited by 22 publications

(23 citation statements)

References 50 publications

(66 reference statements)

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“…The prominent action of IL-17A is attraction of neutrophils to the site of inflammation, generating a powerful immune response [47]. Coculture of healthy human keratinocytes and activated CD4 + or CD8 + T cells that favor a Th17 phenotype increased production of CXCL10 from keratinocytes [48]. Plasma IL-17 levels are also positively correlated with CXCL10 concentrations in patients with SLE [49].…”

Section: Discussionmentioning

confidence: 99%

Differential gene and protein expression of chemokines and cytokines in synovial fluid of patients with arthritis

et al. 2016

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BackgroundPsoriatic arthritis (PsA), an inflammatory musculoskeletal disease, develops in approximately 30% of patients with psoriasis. Previously, chemokine (C-X-C motif) ligand 10 (CXCL10) was identified as a predictive biomarker of PsA in patients with psoriasis and was reduced after development of PsA. The purpose of the present study was to explore messenger RNA (mRNA) and protein expression of CXCL10 and its receptor, chemokine (C-X-C motif) receptor 3 (CXCR3), in the joints of patients with PsA to gain insight into their role in the pathogenesis of the disease.MethodsSera from 47 patients with PsA and 33 healthy control subjects were compared for expression of CXCL10 by Luminex assay. Synovial fluid (SF) was obtained from patients with PsA (n = 40), osteoarthritis (OA; n = 14), gout (n = 8), and rheumatoid arthritis (RA; n = 11) during clinical care. SF mRNA and protein expression of CXCL10, interleukin-17A (IL-17A), CXCR3, TBX21, RORC and/or interferon γ (IFNγ) were compared among the above-mentioned disease groups, as well as in paired SF and serum samples from patients with PsA using real-time polymerase chain reaction and Luminex assays, respectively.ResultsSerum CXCL10 was significantly higher in patients with PsA than in control subjects (p = 0.0007). CXCL10, IL-17A, and TBX21 expression were elevated in SF cells of patients with PsA compared with those of patients with OA and gout, but not those of patients with RA. CXCR3 and RORC were elevated in PsA SF cells compared with all other patient groups. Concordant results were obtained for CXCL10 and IL-17A protein expression. IFNγ was elevated in PsA SF compared with OA SF (p = 0.015). CXCL10 protein expression was substantially increased in SF (median 7283.9 pg/ml, interquartile range [IQR] 1330–10,362 pg/ml) compared with paired serum samples (median 282.06, IQR 180.7–395.8 pg/ml; p = 0.001), whereas IFNγ was significantly reduced (SF median 6.03 pg/ml, IQR 4.47–8.94 pg/ml; versus serum median 23.70 pg/ml, IQR 3.2–104.6 pg/ml; p = 0.001).ConclusionsCXCL10 may have an important etiological role in PsA that is analogous to that in RA, and it is a candidate biomarker to distinguish PsA from healthy individuals and from patients with OA and gout.

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Section: Discussionmentioning

confidence: 99%

Differential gene and protein expression of chemokines and cytokines in synovial fluid of patients with arthritis

et al. 2016

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“…Direct interactions between keratinocytes and T cells are important in the development of psoriasis [45]. The Ras-Rafmitogen-activated protein kinase (MAPK) pathway, which was associated with keratinocyte proliferation, was up-regulated in the hyperplastic epidermis of psoriasis.…”

Section: New Therapeutic Targets For Psoriasismentioning

confidence: 99%

Recent advances in atopic dermatitis and psoriasis: Genetic background, barrier function, and therapeutic targets

Miyagaki

Sugaya

2015

Journal of Dermatological Science

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“…It has recently been found that co-culturing keratinocytes with T cells, keratinocytes pushed T subpopulations toward specific phenotypes such as IL-17+CCR6+RORγt+ (Retinoic acid-related Orphan Receptor γT). Moreover, T lymphocytes isolated from skin are in part IL-17+, confirming that there is a clear intercellular communication between immune T cells and non-immune keratinocyte cells and that any deregulation in the information circulation can trigger skin disease [11]. Keratinocytes, as demonstrated 20 years ago, secrete large quantities of interleukin-1alpha (IL-1alpha), tumor necrosis factor (TNF) and neuropeptides in response to various stimuli (kinetic, thermal trauma, UVB irradiation) [12].…”

Section: Skin’s Immune Systemmentioning

confidence: 99%

“…This molecule’s tandem, chemokine receptor CCR10 and its ligands can be “hijacked” by cancer cells and used for their proliferation and evasion from immune surveillance [19]. Recent experimental data showed that, when culturing human keratinocytes directly with T lymphocytes (CD4+ or CD8+) chemokines like CCL2, CCL20 and CXCL10 are actively secreted [11]. …”

Section: Skin’s Immune Systemmentioning

confidence: 99%

Immunomics in Skin Cancer - Improvement in Diagnosis, Prognosis and Therapy Monitoring

Bulman¹,

Neagu²,

Constantin

2013

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This review will focus on the elements of the skin’s immune system, immune cells and/or non-immune cells that support immune mechanisms, molecules with immune origin and/or immune functions that are involved in skin carcinogenesis. All these immune elements are compulsory in the development of skin tumors and/or sustainability of the neoplastic process. In this light, recent data gathered in this review will acknowledge all immune elements that contribute to skin tumorigenesis; moreover, they can serve as immune biomarkers. These immune markers can contribute to the diagnostic improvement, prognosis forecast, therapy monitoring, and even personalized therapeutical approach in skin cancer. Immune processes that sustain tumorigenesis in non-melanoma and melanoma skin cancers are described in the framework of recent data.

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Co-culture of healthy human keratinocytes and T-cells promotes keratinocyte chemokine production and RORγt-positive IL-17 producing T-cell populations

Cited by 22 publications

References 50 publications

Differential gene and protein expression of chemokines and cytokines in synovial fluid of patients with arthritis

Differential gene and protein expression of chemokines and cytokines in synovial fluid of patients with arthritis

Recent advances in atopic dermatitis and psoriasis: Genetic background, barrier function, and therapeutic targets

Immunomics in Skin Cancer - Improvement in Diagnosis, Prognosis and Therapy Monitoring

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