Resident cutaneous memory T cells: a clinical review of their role in chronic inflammatory dermatoses and potential as therapeutic targets

Pham, James P; Wark, Kirsty J L; Woods, Jane; Frew, John W

doi:10.1093/bjd/ljad303

Cited by 8 publications

(2 citation statements)

References 95 publications

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“…In the skin, T cells play important roles in protective immunity and the development of inflammatory and autoimmune diseases [ 63 , 64 , 65 ]. Several studies have examined the role of 1,25(OH) 2 D and the VDR in T-cell development, differentiation, and function.…”

Section: Effect Of 125(oh) 2 D On Cells In the Skinmentioning

confidence: 99%

Vitamin D in Cutaneous T-Cell Lymphoma

Ødum,

Geisler

2024

Cells

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Cutaneous T-cell lymphoma (CTCL) is characterized by the proliferation of malignant T cells in inflamed skin lesions. Mycosis fungoides (MF)—the most common variant of CTCL—often presents with skin lesions around the abdomen and buttocks (“bathing suit” distribution), i.e., in skin areas devoid of sun-induced vitamin D. For decades, sunlight and vitamin D have been connected to CTCL. Thus, vitamin D induces apoptosis and inhibits the expression of cytokines in malignant T cells. Furthermore, CTCL patients often display vitamin D deficiency, whereas phototherapy induces vitamin D and has beneficial effects in CTCL, suggesting that light and vitamin D have beneficial/protective effects in CTCL. Inversely, vitamin D promotes T helper 2 (Th2) cell specific cytokine production, regulatory T cells, tolerogenic dendritic cells, as well as the expression of immune checkpoint molecules, all of which may have disease-promoting effects by stimulating malignant T-cell proliferation and inhibiting anticancer immunity. Studies on vitamin D treatment in CTCL patients showed conflicting results. Some studies found positive effects, others negative effects, while the largest study showed no apparent clinical effect. Taken together, vitamin D may have both pro- and anticancer effects in CTCL. The balance between the opposing effects of vitamin D in CTCL is likely influenced by treatment and may change during the disease course. Therefore, it remains to be discovered whether and how the effect of vitamin D can be tilted toward an anticancer response in CTCL.

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Section: Effect Of 125(oh) 2 D On Cells In the Skinmentioning

confidence: 99%

Vitamin D in Cutaneous T-Cell Lymphoma

Ødum,

Geisler

2024

Cells

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“…Several studies have found the presence of a “molecular scar” in resolved skin, which may be involved in disease relapse [ 16 , 17 ]. Pathogenic tissue-resident memory T-cells (TRMs) have been proposed as key players in disease memory in psoriasis and other chronic skin diseases [ 18 , 19 , 20 ]. TRMs are dependent on interaction with the local microenvironment, and specifically the pluripotent cytokine transforming growth factor beta (TGFbeta), the metabolic factors fatty-acid-binding proteins 4 and 5, and the cytokines IL-7 and IL-15 are involved in the differentiation and maintenance of TRMs [ 21 , 22 , 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Secukinumab and Dead Sea Climatotherapy Impact Resolved Psoriasis Skin Differently Potentially Affecting Disease Memory

Emmanuel,

Ignatov,

Bertelsen

et al. 2024

IJMS

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Secukinumab and Dead Sea treatment result in clear skin for many psoriasis patients, through distinct mechanisms. However, recurrence in the same areas after treatments suggests the existence of a molecular scar. We aimed to compare the molecular and genetic differences in psoriasis patients who achieved complete response from secukinumab and Dead Sea climatotherapy treatments. We performed quantitative immunohistochemical and transcriptomic analysis, in addition to digital spatial profiling of skin punch biopsies. Histologically, both treatments resulted in a normalization of the lesional skin to a level resembling nonlesional skin. Interestingly, the transcriptome was not normalized by either treatments. We revealed 479 differentially expressed genes between secukinumab and Dead Sea climatotherapy at the end of treatment, with a psoriasis panel identifying SERPINB4, SERPINB13, IL36G, IL36RN, and AKR1B10 as upregulated in Dead Sea climatotherapy compared with secukinumab. Using digital spatial profiling, pan-RAS was observed to be differentially expressed in the microenvironment surrounding CD103+ cells, and IDO1 was differentially expressed in the dermis when comparing the two treatments. The differences observed between secukinumab and Dead Sea climatotherapy suggest the presence of a molecular scar, which may stem from mechanistically different pathways and potentially contribute to disease recurrence. This may be important for determining treatment response duration and disease memory.

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Atopic dermatitis: pathogenesis and therapeutic intervention

Yue,

Zhou,

Wang

et al. 2024

MedComm

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The skin serves as the first protective barrier for nonspecific immunity and encompasses a vast network of skin‐associated immune cells. Atopic dermatitis (AD) is a prevalent inflammatory skin disease that affects individuals of all ages and races, with a complex pathogenesis intricately linked to genetic, environmental factors, skin barrier dysfunction as well as immune dysfunction. Individuals diagnosed with AD frequently exhibit genetic predispositions, characterized by mutations that impact the structural integrity of the skin barrier. This barrier dysfunction leads to the release of alarmins, activating the type 2 immune pathway and recruiting various immune cells to the skin, where they coordinate cutaneous immune responses. In this review, we summarize experimental models of AD and provide an overview of its pathogenesis and the therapeutic interventions. We focus on elucidating the intricate interplay between the immune system of the skin and the complex regulatory mechanisms, as well as commonly used treatments for AD, aiming to systematically understand the cellular and molecular crosstalk in AD‐affected skin. Our overarching objective is to provide novel insights and inform potential clinical interventions to reduce the incidence and impact of AD.

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Resident cutaneous memory T cells: a clinical review of their role in chronic inflammatory dermatoses and potential as therapeutic targets

Cited by 8 publications

References 95 publications

Vitamin D in Cutaneous T-Cell Lymphoma

Vitamin D in Cutaneous T-Cell Lymphoma

Secukinumab and Dead Sea Climatotherapy Impact Resolved Psoriasis Skin Differently Potentially Affecting Disease Memory

Atopic dermatitis: pathogenesis and therapeutic intervention

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