Functional heterogeneity of human skin‐resident memory T cells in health and disease

Strobl, Johanna; Haniffa, Muzlifah

doi:10.1111/imr.13213

Cited by 9 publications

(3 citation statements)

References 241 publications

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“…Further implicating TRMs in disease pathogenesis, studies have observed that the TCR sequence from fixed drug eruption patient T-cells derive from local cytotoxic TRMs rather than the central memory pool ( Strobl and Haniffa, 2023 ). Additionally, TCR repertoire analysis in TEN patients revealed massive clonal expansion of CD8 + lymphocytes which derive from a TEM phenotype, providing further supporting evidence of their involvement ( Villani et al, 2021 ).…”

Section: Why the Skin?mentioning

confidence: 99%

Why drug exposure is frequently associated with T-cell mediated cutaneous hypersensitivity reactions

Line,

Saville,

Meng

et al. 2023

Front. Toxicol.

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Cutaneous hypersensitivity reactions represent the most common manifestation of drug allergy seen in the clinic, with 25% of all adverse drug reactions appearing in the skin. The severity of cutaneous eruptions can vastly differ depending on the cellular mechanisms involved from a minor, self-resolving maculopapular rash to major, life-threatening pathologies such as the T-cell mediated bullous eruptions, i.e., Stevens Johnson syndrome/toxic epidermal necrolysis. It remains a significant question as to why these reactions are so frequently associated with the skin and what factors polarise these reactions towards more serious disease states. The barrier function which the skin performs means it is constantly subject to a barrage of danger signals, creating an environment that favors elicitation. Therefore, a critical question is what drives the expansion of cutaneous lymphocyte antigen positive, skin homing, T-cell sub-populations in draining lymph nodes. One answer could be the heterologous immunity hypothesis whereby tissue resident memory T-cells that express T-cell receptors (TCRs) for pathogen derived antigens cross-react with drug antigen. A significant amount of research has been conducted on skin immunity in the context of contact allergy and the role of tissue specific antigen presenting cells in presenting drug antigen to T-cells, but it is unclear how this relates to epitopes derived from circulation. Studies have shown that the skin is a metabolically active organ, capable of generating reactive drug metabolites. However, we know that drug antigens are displayed systemically so what factors permit tolerance in one part of the body, but reactivity in the skin. Most adverse drug reactions are mild, and skin eruptions tend to be visible to the patient, whereas minor organ injury such as transient transaminase elevation is often not apparent. Systemic hypersensitivity reactions tend to have early cutaneous manifestations, the progression of which is halted by early diagnosis and treatment. It is apparent that the preference for cutaneous involvement of drug hypersensitivity reactions is multi-faceted, therefore this review aims to abridge the findings from literature on the current state of the field and provide insight into the cellular and metabolic mechanisms which may contribute to severe cutaneous adverse reactions.

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Section: Why the Skin?mentioning

confidence: 99%

Why drug exposure is frequently associated with T-cell mediated cutaneous hypersensitivity reactions

Line,

Saville,

Meng

et al. 2023

Front. Toxicol.

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“…Recent studies highlighted the involvement of resident memory T cells (T RM ) in disease pathogenesis [ 24 , 27 , 29 – 31 ]. T RM are long-lived memory T cells that persist in tissues like the skin and are characterized by a specific transcriptional program [ 32 , 33 ]. They express characteristic cell surface markers involved in their retention in the tissue, such as CD69, CD103, or CD49a, the latter marker defining a subset of T RM cells with cytotoxic properties [ 29 , 34 – 36 ].…”

Section: Introductionmentioning

confidence: 99%

“…It is now clear that the micro environment plays a crucial role in the formation and regulation of T RM . Indeed, the expression of CD103 is dependent on transforming growth factor (TGF)-β [ 36 ], and a growing number of studies reported the involvement of several pro-inflammatory cytokines involved in T RM homeostasis, such as IL-15, IL-12, IL-18, IL-33, IFNγ, TNFα [ 32 ]. The presence of T RM in vitiligo skin is undoubtedly linked to the recurrence of lesions on previously affected anatomical sites that have repigmented following treatment [ 37 ], as shown in psoriasis or atopic dermatitis [ 38 – 40 ].…”

Section: Introductionmentioning

confidence: 99%

Aetiopathogenesis of Vitiligo

Boniface

2023

Dermatol Pract Concept

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Vitiligo is a chronic auto-immune disease characterized by skin depigmentation due to the loss of melanocytes. The better understanding of the disease mechanisms is currently undergoing a significant dynamism, opening a new era in therapeutic development. The pathophysiology of vitiligo has attracted the attention of researchers for years and many advances have been made in clarifying the crosstalk between the cellular players involved in the development of vitiligo lesions. The understanding of the complex interactions between epidermal cells (i.e. melanocytes and keratinocytes), dermal fibroblasts, and immune cells, led to a better characterization of the signals leading to the loss of melanocytes. Recent advances highlighted the role resident T memory cells in the development and recurrence of lesions. This narrative review aims to give an overview of the mechanisms leading to melanocyte disappearance in vitiligo, with a focus on the intercellular interaction network involved in the activation of the local skin immune response.

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Inflammation, Immunology and Allergy

Haniffa

2024

Rook's Textbook of Dermatology

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The skin is the largest barrier organ in the human body. The anatomy and composition of the human skin enables it to perform its function to protect us from external environmental challenges, including ultraviolet irradiation, temperature variation, mechanical force and microbial challenge. This chapter details our understanding of the cellular components of the human skin including the immune cells that form the skin immune network in health, following perturbation and skin disease. We chart the advancement in our knowledge of the human skin through the application of a range of technological platforms from immunohistochemistry to cutting‐edge single cell and spatial omics technologies. The chapter summarises our understanding of how the skin immune network interfaces with systemic immune responses via the peripheral blood circulation and lymphatic drainage from the skin to draining lymph nodes. In addition, we address the differences between the human and mouse skin immune networks, the role of the microbiota in health and disease as well as recent concepts of inflammation that have altered our understanding of homeostasis, repair and healing and disease.

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Functional heterogeneity of human skin‐resident memory T cells in health and disease

Cited by 9 publications

References 241 publications

Why drug exposure is frequently associated with T-cell mediated cutaneous hypersensitivity reactions

Why drug exposure is frequently associated with T-cell mediated cutaneous hypersensitivity reactions

Aetiopathogenesis of Vitiligo

Inflammation, Immunology and Allergy

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