Resident memory and recirculating memory T cells cooperate to maintain disease in a mouse model of vitiligo

Richmond, JM; Strassner, James P.; Rashighi, M; Agarwal, P; Garg, M; Essien, KI; LS, Pell; Harris, J.E.

doi:10.21417/b7v884

Cited by 17 publications

(32 citation statements)

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“…Vitiligo-affected skin was shown to have CD8 + T cells recognizing tumor/self-antigens and to exhibit a T RM cell phenotype (CD44 hi CD62L lo CD69 + CD103 + ). In line with this, autoreactive CD8 + T cells with a CD69 + CD103 ± T RM phenotype have been found in the skin of vitiligo patients (Boniface et al, 2018;Cheuk et al, 2017;Richmond, Strassner, Rashighi, et al, 2018;Richmond, Strassner, Zapata, et al, 2018) (Figure 2). Compared to healthy unaffected donor or psoriasis skin, lesional skin from vitiligo patients was shown to be enriched with CD49a + CD103 + CD8 + (Cheuk et al, 2017) and CD69 + CD103 ± CD8 + T RM cells, independent of disease activity (Boniface et al, 2018).…”

Section: T Rm Cells In the Pathogenesis Of Vitiligosupporting

confidence: 71%

“…Likewise, skin CD8 + T RM cells lacked PD-1 expression in a murine model of viral infection (Jiang et al, 2012). In a vitiligo mouse model, however, autoreactive CD8 + T RM cells did express PD-1 (Richmond, Strassner, Rashighi, et al, 2018).…”

Section: Expression Of Immune Checkpoints By Resident Memory-expresmentioning

confidence: 95%

“…These cells can develop not only after pathogen infection, but also after sensitization to otherwise harmless environmental or self-antigens (Clark, 2015). The involvement of T RM cells has been demonstrated in various skin diseases, such as psoriasis (Cheuk et al, 2014;Clark, 2011;Matos et al, 2017;Suarez-Farinas, Fuentes-Duculan, Lowes, & Krueger, 2011), fixed drug eruptions (Shiohara, 2009), allergic contact dermatitis (Gaide et al, 2015;Honda, Egawa, Grabbe, & Kabashima, 2013), cutaneous T-cell lymphoma-a malignancy of T RM cells (Campbell, Clark, Watanabe, & Kupper, 2010) and vitiligo (Boniface et al, 2018;Cheuk et al, 2017;Richmond, Strassner, Rashighi, et al, 2018;Richmond, Strassner, Zapata, et al, 2018).…”

mentioning

confidence: 99%

“…Conversely, vitiligo patients have threefold lower probability of developing melanoma during their life span than non-vitiligo patients (Paradisi et al, 2014;Teulings et al, 2013). Recent work has indicated the pathogenic involvement of T RM cells in human vitiligo (Boniface et al, 2018;Cheuk et al, 2017;Richmond, Strassner, Rashighi, et al, 2018;Richmond, Strassner, Zapata, et al, 2018) and data on this are still emerging. Other studies have demonstrated a protective role for T RM cells in melanoma (Boddupalli et al, 2016;Edwards et al, 2018;Enamorado et al, 2017;Gálvez-Cancino et al, 2018;Malik et al, 2017;Murray et al, 2016;Park, Buzzai, et al, 2018).…”

mentioning

confidence: 99%

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Skin‐resident memory T cells as a potential new therapeutic target in vitiligo and melanoma

Willemsen

Linkutė

Luiten

et al. 2019

Pigment Cell Melanoma Res

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Tissue‐resident memory T (TRM) cells are abundant in the memory T cell pool and remain resident in peripheral tissues, such as the skin, where they act as alarm sensors or cytotoxic killers. TRM cells persist long after the pathogen is eliminated and can respond rapidly upon reinfection with the same antigen. When aberrantly activated, skin‐located TRM cells have a profound role in various skin disorders, including vitiligo and melanoma. Autoreactive TRM cells are present in human lesional vitiligo skin and mouse models of vitiligo, which suggests that targeting these cells could be effective as a durable treatment strategy for vitiligo. Furthermore, emerging evidence indicates that induction of melanoma‐reactive TRM cells is needed to achieve effective protection against tumor growth. This review highlights seminal reports about skin‐resident T cells, focusing mainly on their role in the context of vitiligo and melanoma, as well as their potential as therapeutic targets in both diseases.

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Section: T Rm Cells In the Pathogenesis Of Vitiligosupporting

confidence: 71%

Section: Expression Of Immune Checkpoints By Resident Memory-expresmentioning

confidence: 95%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Skin‐resident memory T cells as a potential new therapeutic target in vitiligo and melanoma

Willemsen

Linkutė

Luiten

et al. 2019

Pigment Cell Melanoma Res

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“…To test this hypothesis, we infected aged mice with PR8 virus and then injected the mice with high or low doses of CD8 depleting antibody (α-CD8) at 21 d.p.i. to deplete CD8 + T cells systemically in lymphoid and peripheral tissues (high dose) or only in lymphoid organs and the circulation (low dose) [40, 47, 48] (Figure 6A). Both low dose and high dose CD8 Ab treatment largely ablated splenic CD8 + T cells, however, only high dose CD8 Ab injection caused significant ablation of CD8 + T cells in the lung parenchyma (Figure 6B and S6A).…”

Section: Resultsmentioning

confidence: 99%

Tissue-resident CD8⁺T cells drive age-associated chronic lung sequelae following viral pneumonia

Sun

Goplen

2020

Preprint

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32Lower respiratory viral infections, such as influenza virus and severe acute respiratory syndrome 33 coronavirus 2 (SARS-CoV2) infections, often cause severe viral pneumonia in aged individuals. 34Here, we report that influenza viral pneumonia leads to chronic non-resolving lung pathology 35 and exaggerated accumulation of CD8 + tissue-resident memory T cells (TRM) in the respiratory 36 tract of aged hosts. TRM accumulation relies on elevated TGF-b present in aged tissues. Further, 37we show that TRM isolated from aged lungs lack a subpopulation characterized by expression of 38 molecules involved in TCR signaling and effector function. Consequently, TRM cells from aged 39 lungs were insufficient to provide heterologous protective immunity. Strikingly, the depletion of 40 CD8 + TRM cells dampens persistent chronic lung inflammation and ameliorates tissue fibrosis in 41 aged, but not young, animals. Collectively, our data demonstrate that age-associated TRM cell 42 malfunction supports chronic lung inflammatory and fibrotic sequelae following viral pneumonia 43 in aged hosts. 44 45 46 47 48

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Association of Anti–Programmed Cell Death 1 Cutaneous Toxic Effects With Outcomes in Patients With Advanced Melanoma

et al. 2019

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Immune checkpoint inhibitors block key mediators of immune tolerance, producing antitumor responses and autoimmunelike toxic effects. 1 Toxic effects indicate immune activation against host tissues, although it remains controversial whether this offtarget activity indicates concurrent antitumor immunity. [2][3][4] Herein, we retrospectively studied whether cutaneous toxic effects correlated with outcomes in patients with advanced melanoma treated with immune checkpoint inhibitors.Methods | We reviewed electronic medical records of patients treated with anti-programmed cell death 1 (anti-PD-1) with or without ipilimumab from a single center. We assessed demographics, cutaneous toxic effects, steroid administration, and outcomes by retrospective review. The Vanderbilt University Medical Center institutional review board approved the study, with a waiver of patient consent.Results | Among 318 patients (202 men [63%]; median [range] age, 63 [22-89] years) from a single center, 120 (38%) who developed cutaneous toxic effects were more likely to have received combination ipilimumab-nivolumab; had similar age, sex, stage, lactate dehydrogenase (LDH) levels; and had prior systemic therapies, including immune or targeted therapies, compared with those without cutaneous toxic effects (Table ). Patients with cutaneous toxic effects had superior response rate (RR) (60.0% vs 28.6%; χ 2 P < .001), progression-free survival (PFS) (median, 797 vs 112 days; log rank P < .001), and overall survival (OS) (median, 1691 vs 526 days; P < .001) (Figure, A)

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Resident memory and recirculating memory T cells cooperate to maintain disease in a mouse model of vitiligo

Cited by 17 publications

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Skin‐resident memory T cells as a potential new therapeutic target in vitiligo and melanoma

Skin‐resident memory T cells as a potential new therapeutic target in vitiligo and melanoma

Tissue-resident CD8⁺T cells drive age-associated chronic lung sequelae following viral pneumonia

Association of Anti–Programmed Cell Death 1 Cutaneous Toxic Effects With Outcomes in Patients With Advanced Melanoma

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Resident memory and recirculating memory T cells cooperate to maintain disease in a mouse model of vitiligo

Cited by 17 publications

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Skin‐resident memory T cells as a potential new therapeutic target in vitiligo and melanoma

Skin‐resident memory T cells as a potential new therapeutic target in vitiligo and melanoma

Tissue-resident CD8+T cells drive age-associated chronic lung sequelae following viral pneumonia

Association of Anti–Programmed Cell Death 1 Cutaneous Toxic Effects With Outcomes in Patients With Advanced Melanoma

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Tissue-resident CD8⁺T cells drive age-associated chronic lung sequelae following viral pneumonia