Increased frequency of activated CD8+ T cell effectors in patients with psoriatic arthritis

Diani, Marco; Casciano, Fabio; Marongiu, Laura; Longhi, Matteo; Altomare, A.; Pigatto, Paolo D.; Secchiero, Paola; Gambari, Roberto; Banfi, Giuseppe; Manfredi, Angelo A.; Altomare, G. F.; Granucci, Francesca; Reali, Eva

doi:10.1038/s41598-019-47310-5

Cited by 53 publications

(57 citation statements)

References 33 publications

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“…In accordance with the accumulation of neutrophils in psoriasis, the gene expression of neutrophilic cytochemokines CXCL1, CXCL2, CXCL8, and IL-36 is upregulated in the lesional skin of psoriasis [68,[155][156][157]. Psoriatic keratinocytes produce a large amount of CCL20 [158,159], which is a potent chemoattractant for CCR6 + IL-17A-producing Th17 [89,143,160], ILC3 [161,162], Tc17 [163,164], and γδ T cells [78,165]. Interestingly, IL-17A actively upregulates the production of these key cytochemokines as well as proliferative capacity in keratinocytes.…”

Section: Il-17a and Psoriasismentioning

confidence: 93%

“…While most chemokines redundantly bind to multiple receptors, CCL20 has only one known receptor, CCR6 [191]. CCR6 is expressed on dendritic cells [159] and IL-17-producing immune cells, including Th17 [89,143,201], ILC3 [161,162], Tc17 [163,164], and γδ T cells [78,165]. CCR6 is now considered a representative marker for Th17 cells [202,203].…”

Section: Il-17a and Cyto/chemokines In Keratinocytesmentioning

confidence: 99%

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Interleukin-17A and Keratinocytes in Psoriasis

Furue

Tsuji

et al. 2020

IJMS

176

155

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The excellent clinical efficacy of anti-interleukin 17A (IL-17A) biologics on psoriasis indicates a crucial pathogenic role of IL-17A in this autoinflammatory skin disease. IL-17A accelerates the proliferation of epidermal keratinocytes. Keratinocytes produce a myriad of antimicrobial peptides and chemokines, such as CXCL1, CXCL2, CXCL8, and CCL20. Antimicrobial peptides enhance skin inflammation. IL-17A is capable of upregulating the production of these chemokines and antimicrobial peptides in keratinocytes. CXCL1, CXCL2, and CXCL8 recruit neutrophils and CCL20 chemoattracts IL-17A-producing CCR6+ immune cells, which further contributes to forming an IL-17A-rich milieu. This feed-forward pathogenic process results in characteristic histopathological features, such as epidermal hyperproliferation, intraepidermal neutrophilic microabscess, and dermal CCR6+ cell infiltration. In this review, we focus on IL-17A and keratinocyte interaction regarding psoriasis pathogenesis.

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Section: Il-17a and Psoriasismentioning

confidence: 93%

Section: Il-17a and Cyto/chemokines In Keratinocytesmentioning

confidence: 99%

Interleukin-17A and Keratinocytes in Psoriasis

Furue

Tsuji

et al. 2020

IJMS

176

155

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“…CCR6 is a representative surface marker for IL-17A-producing immune cells [19][20][21]23,28,43]. CCL20 and CCR6 engagement is critical for the recruitment of CCR6 + Th17 cells [27,29,44].…”

Section: Discussionmentioning

confidence: 99%

“…The recruitment of Th17 cells into the lesion is governed by CCL20-CCR6 engagement [19,20]. The expression of CCR6 has been confirmed in other IL-17A-producing cytotoxic T cells (Tc17) [21,22], innate lymphoid cell group3 (ILC3) [23,24], and γδT cells [25,26]. CCL20 is a potent chemoattractant for CCR6 + T cells as well as dendritic cells [20,[27][28][29].…”

Section: Introductionmentioning

confidence: 93%

The EGFR-ERK/JNK-CCL20 Pathway in Scratched Keratinocytes May Underpin Koebnerization in Psoriasis Patients

Furue

Ito

Tanaka

et al. 2020

IJMS

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Epidermal keratinocytes represent a rich source of C-C motif chemokine 20 (CCL20) and recruit CCR6+ interleukin (IL)-17A–producing T cells that are known to be pathogenic for psoriasis. A previous study revealed that scratch injury on keratinocytes upregulates CCL20 production, which is implicated in the Koebner phenomenon characteristically seen in psoriasis patients. However, the molecular mechanisms leading to scratch-induced CCL20 production remain elusive. In this study, we demonstrate that scratch injury upregulates the phosphorylation of epidermal growth factor receptor (EGFR) and that the specific EGFR inhibitor PD153035 attenuates scratch-induced CCL20 upregulation in an extracellular signal-related kinase (ERK)-dependent, and to a lesser extent, a c-Jun N-terminal kinase (JNK)-dependent but p38 mitogen-activated protein kinase (MAPK)–independent manner. Immunoreactive CCL20 was visualized in the keratinocytes that lined the scratched wound. IL-17A also induced the phosphorylation of EGFR and further augmented scratch-induced CCL20 upregulation. The EGFR-ERK/JNK-CCL20 pathway in scratched keratinocytes may explain why Koebnerization is frequently seen in psoriasis patients.

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“…Their egression into the periphery may indicate the importance of other circulating antigens in the pathogenesis of IBD. Furthermore, spondylarthropathic disorders, including psoriatic arthritis have also been recently characterized by an increased frequency of circulating CD8+ CD69+ T cells compared to psoriasis and healthy controls (Diani et al 2019).…”

Section: Discussionmentioning

confidence: 99%

Specific T-Cell Subsets Can Predict the Efficacy of Anti-TNF Treatment in Inflammatory Bowel Diseases

Dulic

Toldi

Sava

et al. 2020

Arch. Immunol. Ther. Exp.

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The effect of TNF-blockers on T-lymphocyte subsets is largely unknown in inflammatory bowel diseases (IBDs). The aim of the present study was to analyze the prevalence of T-cell subtypes and their correlation to therapeutic response. Sixtyeight patients with Crohn's disease (CD), 46 with ulcerative colitis (UC) were enrolled. (1) The clinical course was followed after the initiation of TNF-blockers (prospective study). (2) The immunophenotype was also compared between long-term anti-TNF treated-responders and non-responders (cross-sectional study). The results were compared with those of therapynaïve patients with active disease and those in remission with non-biological immunosuppressive therapy, and with healthy controls. Fourteen subtypes of peripheral blood T cells were measured with flow cytometry. The prevalence of Th2 and Th17 cells, of HLA-DR-and CD69-positive CD4 and CD8 cells, was higher, whereas the percentage of CD45RA-positive CD4 and CD8 cells was lower in both IBDs than in controls. CD8CD69 cell frequency was lower in remission, and decreased during anti-TNF therapy in CD responders. CD8CD45RO memory cells had higher prevalence in UC non-responders than in those starting anti-TNF. CD4CD45RO percentage < 49.05 at the initiation of TNF-blockers was predictive of a subsequent therapeutic response in CD, and Th2 and Th17 prevalence correlated with the duration of remission on TNF-blockers in UC. This study provided a detailed description of the T-cell composition in IBDs. CD8CD69 prevalence may be an activity marker in CD, and CD4CD45RO, Th2 and Th17 levels could be predictive for a therapeutic response to anti-TNF.

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Increased frequency of activated CD8+ T cell effectors in patients with psoriatic arthritis

Cited by 53 publications

References 33 publications

Interleukin-17A and Keratinocytes in Psoriasis

Interleukin-17A and Keratinocytes in Psoriasis

The EGFR-ERK/JNK-CCL20 Pathway in Scratched Keratinocytes May Underpin Koebnerization in Psoriasis Patients

Specific T-Cell Subsets Can Predict the Efficacy of Anti-TNF Treatment in Inflammatory Bowel Diseases

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