Significance of IL-17A-producing CD8+CD103+ skin resident memory T cells in psoriasis lesion and their possible relationship to clinical course

Kurihara, Kenzo; Fujiyama, Toshiharu; Phadungsaksawasdi, Pawit; Ito, Taisuke; Tokura, Y.

doi:10.1016/j.jdermsci.2019.06.002

Cited by 66 publications

(82 citation statements)

References 28 publications

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“…In addition, CD8+ CD103+ TRM cells more frequently produced IL-17A than CD8+ CD103-and effector cells CD8+ CD103 or CD4+ CD103+. Interestingly, the number of CD8+ CD103+ IL-17A + TRM cells in patients treated with biological or systemic therapy was higher [13]. In contrast, in the dermis of the psoriatic plaques, TRM cells show lower expression of CD103, as demonstrated by Cheuk et al [5].…”

Section: Tissue Resident Memory Cells In Psoriasismentioning

confidence: 82%

“…They also secrete granzyme B, which helps to reduce the spread of pathogens at the site of infection. They can activate the innate and adaptive mechanisms of the immune response [2,10,[12][13][14][15]. TRM acts as a bridge between the adaptive and innate immune systems.…”

Section: Tissue Resident Memory Cells (Trm)mentioning

confidence: 99%

“…The CD103 marker (integrin αE subunit) is only expressed on CD8+ TRM cells, not CD4+ TRM. Its expression is most prominent on epidermal CD4+ and CD8+ TRM cells because it enables TRM binding to E-cadherin, which is widely expressed by epithelial cells [8,13,18]. The CD69 marker plays a key role in distinguishing T cells in tissues from those in circulation and it is responsible for the colonization of these cells in tissues, preventing them from recirculating.…”

Section: Tissue Resident Memory Cells (Trm)mentioning

confidence: 99%

“…In the study of Kurihara et al [13], biopsies from psoriatic lesions were examined. The number of CD8+CD103+ TRM cells in the epidermis correlated with the thickness of the epidermis (p = 0.016), suggesting their role in the formation of psoriatic lesions [13]. They were mostly CD8+ CD69+ T cells, expressing skin colonization antigens, and the count of CD4+ CD103+ TRM was low.…”

Section: Tissue Resident Memory Cells In Psoriasismentioning

confidence: 99%

“…One of the reasons is its resistance to apoptosis. The heterodimeric marker molecule CD8+ (αEβ7) consists of CD103 and β7 subunits and plays a key role in the stability of CD8+ TRM cells by increasing the level of the Bcl-2 molecule with anti-apoptotic activity [8,13]. In contrast, TRM can produce granzyme B (serine protease), which can induce cellular apoptosis [23].…”

Section: Tissue Resident Memory Cells In Psoriasismentioning

confidence: 99%

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Immunological Memory of Psoriatic Lesions

Owczarczyk‐Saczonek

Krajewska–Włodarczyk

Kasprowicz-Furmańczyk

et al. 2020

IJMS

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The natural course of psoriasis is the appearance of new lesions in the place of previous ones, which disappeared after a successful therapy. Recent studies of psoriasis etiopathogenesis showed that after psoriatic plaques have disappeared, in healthy skin we can still find a trace of inflammation in the form of tissue resident memory cells (TRM). They are originally responsible for protection against viral and bacterial infections in non-lymphatic tissues. In psoriatic inflammation, they are characterized by heterogeneity depending on their origin. CD8+ T cells TRM are abundantly present in psoriatic epidermis, while CD4+ TRM preferentially populate the dermis. In psoriasis, epidermal CD8+ TRM cells express CLA, CCR6, CD103 and IL-23R antigen and produce IL-17A during ex vivo stimulation. However, CD4+ CD103+ TRM can also colonize the epidermis and produce IL-22 during stimulation. Besides T cells, Th22 and epidermal DCs proved that epidermal cells in healed skin were still present and functioning after several years of disease remission. It explains the clinical phenomenon of the tendency of psoriatic lesions to relapse in the same location and it allows to develop new therapeutic strategies in the future.

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Section: Tissue Resident Memory Cells In Psoriasismentioning

confidence: 82%

Section: Tissue Resident Memory Cells (Trm)mentioning

confidence: 99%

Section: Tissue Resident Memory Cells (Trm)mentioning

confidence: 99%

Section: Tissue Resident Memory Cells In Psoriasismentioning

confidence: 99%

Section: Tissue Resident Memory Cells In Psoriasismentioning

confidence: 99%

See 3 more Smart Citations

Immunological Memory of Psoriatic Lesions

Owczarczyk‐Saczonek

Krajewska–Włodarczyk

Kasprowicz-Furmańczyk

et al. 2020

IJMS

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Noninferiority of 16-Week vs 8-Week Guselkumab Dosing in Super Responders for Maintaining Control of Psoriasis

Eyerich,

Asadullah,

Pinter

et al. 2024

JAMA Dermatol

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ImportancePsoriasis is a chronic inflammatory skin disease with unmet needs for tailored treatment and therapy de-escalation strategies.ObjectiveTo evaluate early intervention with and prolonging the dosing interval for guselkumab, a p19 subunit-targeted interleukin (IL)-23 inhibitor, in patients with moderate to severe psoriasis.Design, Setting, and ParticipantsThe GUIDE clinical trial is an ongoing phase 3b, randomized, double-blinded trial conducted across 80 centers in Germany and France comprising 3 parts evaluating the impact of early disease intervention, prolonged dosing interval, and maintenance of response following treatment withdrawal among adults with moderate to severe plaque psoriasis. In study part 2, reported herein, first and last patient visits were September 2019 and March 2022, respectively.InterventionsIn GUIDE part 1 (week [W]0-W28), patients received guselkumab, 100 mg, at W0, W4, W12, and W20. Those achieving a Psoriasis Area and Severity Index (PASI) of 0 at both W20 and W28 were termed super responders (SRes). In part 2 (W28-W68), SRes were randomized to guselkumab, 100 mg, every 8 weeks or every 16 weeks; non-SRes continued open-label guselkumab every 8 weeks.Main Outcomes and MeasuresPrimary objective was to demonstrate noninferiority (with a 10% margin) of guselkumab every 16 weeks vs every 8 weeks dosing among SRes for maintenance of disease control (PASI &lt;3 at W68). Biomarker substudies assessed immunologic effects in skin and blood.ResultsOverall, 822 patients received guselkumab in part 2 (297 [36.1%] SRes [every 8 weeks/every 16 weeks; n = 148/n = 149] and 525 [63.9%] non-SRes). Among SRes, mean (SD) age was 39.4 (14.1) years, 95 (32.0%) were female, and 202 (68.0%) were male. The primary end point of noninferiority for guselkumab every 16 weeks vs every 8 weeks in SRes was met (P = .001), with 91.9% (137/149; 90% CI, 87.3%-95.3%) of SRes receiving every 16 weeks and 92.6% (137/148; 90% CI, 88.0%-95.8%) of SRes receiving dosing every 8 weeks having PASI lower than 3 at W68. Clinical effects corresponded with immunologic changes; skin CD8-positive tissue-resident memory T (TRM)–cell count decreased quickly from baseline, remaining low in both dosing groups. Similarly, serum IL-17A, IL-17F, IL-22, and β defensin (BD)–2 levels decreased significantly from baseline, remaining low in both dosing groups to W68. Guselkumab was well-tolerated; no new safety signals were identified.Conclusions and RelevancePsoriasis treatment guidelines lack or provide inconsistent advice on patient stratification and treatment de-escalation. We present the first randomized trial providing evidence that, in patients with early complete skin clearance at 2 consecutive visits (W20 and W28), extending the guselkumab dosing interval may control disease activity.Trial RegistrationClinicalTrials.gov Identifier: NCT03818035

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Early intervention and disease memory in psoriasis: A literature review

Abdallah

Emmanuel

Bregnhøj

et al. 2022

JEADV Clinical Practice

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Psoriasis is a chronic inflammatory skin disease, in which molecular and cellular changes retain following clinical resolution of psoriatic lesions, a form of disease memory (‘molecular scar’) that may reestablish the psoriatic inflammation. The increasing evidence of the benefits from early intervention in other immune‐mediated diseases prompts the question of whether early systemic intervention, such as biologics, in new‐onset cutaneous psoriasis may lead to improved clinical response and sustained remission by averting an inflammatory disease memory. Herein, we review the current evidence on early intervention and disease memory in psoriasis. The evidence is sparse and inconsistent, although an early intervention within 2 years of disease‐onset may provide a more favourable long‐term prognosis in psoriasis. However, ongoing randomised clinical trials will explore whether early intervention with biologics in new‐onset psoriasis will be an effective treatment strategy, and whether it prevents the molecular and cellular changes potentially underlying the inflammatory disease memory.

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Significance of IL-17A-producing CD8+CD103+ skin resident memory T cells in psoriasis lesion and their possible relationship to clinical course

Cited by 66 publications

References 28 publications

Immunological Memory of Psoriatic Lesions

Immunological Memory of Psoriatic Lesions

Noninferiority of 16-Week vs 8-Week Guselkumab Dosing in Super Responders for Maintaining Control of Psoriasis

Early intervention and disease memory in psoriasis: A literature review

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