Immunomodulatory aged neutrophils are augmented in blood and skin of psoriasis patients

Rodriguez-Rosales, Yessica Alina; Langereis, Jeroen D.; Gorris, Mark A.J.; Reek, J.M.P.A. van den; Fasse, Esther; Netea, Mihai G.; Vries, I. Jolanda M. de; Gomez-Muñoz, Laia; Cranenbroek, Bram van; Körber, Andreas; Sondermann, Wiebke; Joosten, Irma; Jong, E.M.G.J. de; Koenen, Hans J. P. M.

doi:10.1016/j.jaci.2021.02.041

Cited by 38 publications

(30 citation statements)

References 40 publications

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“…We first compared the absolute numbers and percentages of neutrophils in the peripheral blood of psoriasis patients and healthy donors. In line with previous studies ( 18 ), the numbers and percentages of blood neutrophils were greatly increased in psoriasis patients compared to healthy subjects ( Figure 1A ). The absolute numbers of neutrophils were positively correlated with disease activities measured by PASI score ( Figure 1B ).…”

Section: Resultssupporting

confidence: 92%

Enhanced Migratory Ability of Neutrophils Toward Epidermis Contributes to the Development of Psoriasis via Crosstalk With Keratinocytes by Releasing IL-17A

Liu

Shi

et al. 2022

Front. Immunol.

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Microabscess of neutrophils in epidermis is one of the histological hallmarks of psoriasis. The axis of neutrophil–keratinocyte has been thought to play a critical role in the pathogenesis of psoriasis. However, the features and mechanism of interaction between the two cell types remain largely unknown. Herein, we found that blood neutrophils were increased in psoriasis patients, positively correlated with disease severity and highly expressed CD66b, but not CD11b and CD62L compared to healthy controls. Keratinocytes expressed high levels of psoriasis-related inflammatory mediators by direct and indirect interaction with neutrophils isolated from psoriasis patients and healthy controls. The capacity of neutrophils in provoking keratinocytes inflammatory response was comparable between the two groups and is dependent on IL-17A produced by itself. Neutrophils isolated from psoriasis patients displayed more transcriptome changes related to integrin and increased migration capacity toward keratinocytes with high CD11b expression on cell surface. Of interest, neutrophils were more susceptible to keratinocyte stimulation than to fibroblasts and human umbilical vein endothelial cells (HUVECs) in terms of CD11b expression and the production of ROS and NETs. In conclusion, neutrophils from psoriasis patients gain a strong capacity of IL-17A production and integrins expression that possibly facilitates their abilities to promote production of psoriasis-related inflammatory mediators and migration, a phenomenon likely induced by their interaction with keratinocytes but not with fibroblasts. These findings provide a proof-of-concept that development of new drugs targeting migration of neutrophils could be a more specific and safe solution to treat psoriasis.

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Section: Resultssupporting

confidence: 92%

Enhanced Migratory Ability of Neutrophils Toward Epidermis Contributes to the Development of Psoriasis via Crosstalk With Keratinocytes by Releasing IL-17A

Liu

Shi

et al. 2022

Front. Immunol.

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“…But as they age, expression of CD184 increases again favoring return to the bone marrow for clearance 59 . Here we identified a CD10 - CD177 + immature neutrophil subset that resembles the CD10 - CD16 low CD11b low population which has been recently described in the blood of patients with psoriasis, and shown to express CD184 and have low phagocytic ability and ROS production 60 . On the other hand, in other inflammatory settings mimicking sepsis (LPS injections in mice), aged neutrophils were shown to be particularly effective in migration to sites of inflammation and to exhibit a higher phagocytic activity as compared with the subsequently recruited non-aged neutrophils 61 .…”

Section: Discussionmentioning

confidence: 59%

Novel neutrophil subsets associated with sepsis, vascular dysfunction and metabolic alterations identified using systems immunology

Martinelli

Parthasarathy

Kuang

et al. 2022

Preprint

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Sepsis is a life-threatening condition caused by a dysregulated host response to infection. Despite continued efforts to understand the pathophysiology of sepsis, no effective therapies are currently available. While singular components of the aberrant immune response have been investigated, comprehensive studies linking different data layers are lacking. Using an integrated systems immunology approach, we evaluated neutrophil phenotypes and concomitant changes in cytokines and metabolites in sepsis patients. Our findings identify novel differentially expressed immature neutrophil subsets in sepsis patients. These and other subsets correlate with various proteins, metabolites, and lipids, including pentraxin-3, angiopoietin-2 and lysophosphatidylcholines, in sepsis patients. These results enabled the construction of a predictive model based on weighted multi-omics linear regression analysis for patient classification. These findings could help inform earlier patient stratification and treatment options, as well as facilitate future mechanistic studies targeting the trifecta of surface marker expression, cytokines, and metabolites.

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“…Evidence of neutrophil infiltration in lesional skin was earlier reported by Yao et al [ 47 ]. In the early phase of plaque formation, neutrophils infiltrate the dermis of the skin, then migrate to the epidermis and stratum corneum, where they accumulate as pustules or microabscesses [ 78 , 79 ]. Blood transcriptome profiling from two public psoriasis data sets was studied by Rawat et al [ 75 ].…”

Section: Neutrophils and Blood Transcriptome Signature In Psoriasismentioning

confidence: 99%

Transcriptional Basis of Psoriasis from Large Scale Gene Expression Studies: The Importance of Moving towards a Precision Medicine Approach

Krishnan

Kõks

2022

IJMS

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Transcriptome profiling techniques, such as microarrays and RNA sequencing (RNA-seq), are valuable tools for deciphering the regulatory network underlying psoriasis and have revealed large number of differentially expressed genes in lesional and non-lesional skin. Such approaches provide a more precise measurement of transcript levels and their isoforms than any other methods. Large cohort transcriptomic analyses have greatly improved our understanding of the physiological and molecular mechanisms underlying disease pathogenesis and progression. Here, we mostly review the findings of some important large scale psoriatic transcriptomic studies, and the benefits of such studies in elucidating potential therapeutic targets and biomarkers for psoriasis treatment. We also emphasised the importance of looking into the alternatively spliced RNA isoforms/transcripts in psoriasis, rather than focussing only on the gene-level annotation. The neutrophil and blood transcriptome signature in psoriasis is also briefly reviewed, as it provides the immune status information of patients and is a less invasive platform. The application of precision medicine in current management of psoriasis, by combining transcriptomic data, improves the clinical response outcome in individual patients. Drugs tailored to individual patient’s genetic profile will greatly improve patient outcome and cost savings for the healthcare system.

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Immunomodulatory aged neutrophils are augmented in blood and skin of psoriasis patients

Cited by 38 publications

References 40 publications

Enhanced Migratory Ability of Neutrophils Toward Epidermis Contributes to the Development of Psoriasis via Crosstalk With Keratinocytes by Releasing IL-17A

Enhanced Migratory Ability of Neutrophils Toward Epidermis Contributes to the Development of Psoriasis via Crosstalk With Keratinocytes by Releasing IL-17A

Novel neutrophil subsets associated with sepsis, vascular dysfunction and metabolic alterations identified using systems immunology

Transcriptional Basis of Psoriasis from Large Scale Gene Expression Studies: The Importance of Moving towards a Precision Medicine Approach

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