Single-cell sequencing shows cellular heterogeneity of cutaneous lesions in lupus erythematosus

Zheng, Meiling; Hu, Zhiyan; Mei, Xiaole; Ouyang, Lianlian; Song, Yang; Zhou, Wenhui; Kong, Yi; Wu, Ruifang; Rao, S.; Long, Hai; Shi, Wei; Jing, Hui; Lu, Shuang; Wu, Haijing; Jia, Sujie; Lu, Qianjin; Zhao, Ming

doi:10.1038/s41467-022-35209-1

Cited by 32 publications

(18 citation statements)

References 72 publications

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“…Recent work in a murine CLE model suggests that initial skin infiltration with Th2 cells and re‐polarization to Th1 T RM is required for persistence of CLE skin eruptions. Th1‐polarized T RM produce IFN‐γ and maintain their phenotype in disease recurrence 204,209 . As in addition IL‐15‐induced circulating CD4 + T cells with cytotoxic properties were recently found in systemic lupus erythematosus, 210 future studies of skin T cells in CLE may offer interesting insights into epigenetic potential of CD4 + T RM .…”

Section: Trm In Disease Pathogenesismentioning

confidence: 99%

“…Skin lesions can be classified as acute, subacute, and chronic CLE, with further subvariants. Although autoantibodies, B lymphocytes, and innate immune cell types are more central to pathogenesis of CLE, T cells are considered important in disease propagation 204 . Persistence of chronic CLE subtypes with weak response to B cell depletion may be strongly driven by the presence of clonal CD4 + T RM populations 205,206 .…”

Section: Trm In Disease Pathogenesismentioning

confidence: 99%

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

Strobl

Haniffa

2023

Immunological Reviews

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Summary The human skin is populated by a diverse pool of memory T cells, which can act rapidly in response to pathogens and cancer antigens. Tissue‐resident memory T cells (TRM) have been implicated in range of allergic, autoimmune and inflammatory skin diseases. Clonal expansion of cells with TRM properties is also known to contribute to cutaneous T‐cell lymphoma. Here, we review the heterogeneous phenotypes, transcriptional programs, and effector functions of skin TRM. We summarize recent studies on TRM formation, longevity, plasticity, and retrograde migration and contextualize the findings to skin TRM and their role in maintaining skin homeostasis and altered functions in skin disease.

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Section: Trm In Disease Pathogenesismentioning

confidence: 99%

Section: Trm In Disease Pathogenesismentioning

confidence: 99%

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

Strobl

Haniffa

2023

Immunological Reviews

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“…In peripheral blood, no significant differences were observed in the number of Tregs. Recent advancements in scRNA sequencing enabled a study of tissue infiltrating- and resident-Tregs from skin and kidney tissues affected by SLE ( 204 , 205 ). Dunlap et al.…”

Section: Tissue Tregs In Autoimmune Diseasesmentioning

confidence: 99%

Regulatory T cells in peripheral tissue tolerance and diseases

2023

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Maintenance of peripheral tolerance by CD4+Foxp3+ regulatory T cells (Tregs) is essential for regulating autoreactive T cells. The loss of function of Foxp3 leads to autoimmune disease in both animals and humans. An example is the rare, X-linked recessive disorder known as IPEX (Immune Dysregulation, Polyendocrinopathy, Enteropathy X-linked) syndrome. In more common human autoimmune diseases, defects in Treg function are accompanied with aberrant effector cytokines such as IFNγ. It has recently become appreciated that Tregs plays an important role in not only maintaining immune homeostasis but also in establishing the tissue microenvironment and homeostasis of non-lymphoid tissues. Tissue resident Tregs show profiles that are unique to their local environments which are composed of both immune and non-immune cells. Core tissue-residence gene signatures are shared across different tissue Tregs and are crucial to homeostatic regulation and maintaining the tissue Treg pool in a steady state. Through interaction with immunocytes and non-immunocytes, tissue Tregs exert a suppressive function via conventional ways involving contact dependent and independent processes. In addition, tissue resident Tregs communicate with other tissue resident cells which allows Tregs to adopt to their local microenvironment. These bidirectional interactions are dependent on the specific tissue environment. Here, we summarize the recent advancements of tissue Treg studies in both human and mice, and discuss the molecular mechanisms that maintain tissue homeostasis and prevent pathogenesis.

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“…Lupus erythematosus (LE) is a chronic autoimmune disease that is divided into 2 main clinical types. CLE presents as cellular heterogeneity of lesions that remain localized to the skin or mucosa, and discoid lupus erythematosus (DLE) accounts for >80% of such cases [ 3 ]. SLE involves manifestations, including cutaneous lupus, polyarthritis, nephritis, seizures, leukopenia, and cognitive impairment [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…4.92 nmol/L; reference range 0.98-2.33 nmol/L), thyroxine (T4) (158.47 nmol/L; reference range 62.68-150.84 nmol/L), free triiodothyronine (FT3) (5.77 pmol/L; reference range 2.43-6.01 pmol/L), free thyroxine (FT4) (28.65 pmol/L; reference range 9.01-19.05 pmol/L), thyrotropin (<0.004 µIU/ml; reference range 0.350-4.940 µIU/mL), and TSH-R-Ab concentration (33.94 IU/L; reference range 0.00-1.75 IU/L) 3 ,. anterior and posterior diameter of the isthmus 1.5 cm) with irregular echo and increased blood flow signal.…”

mentioning

confidence: 99%

A 30-Year-Old Woman with a History of Autoimmune Hyperthyroidism Presenting with Fever and Oral Ulcers, Diagnosed with Discoid Lupus Erythematosus

et al. 2023

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Unusual clinical course Background:Lupus erythematosus (LE) is mainly clinically divided into cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) depending on the presence of multi-system manifestations. The most common subtype of CLE is discoid lupus erythematosus (DLE). Graves' disease (GD) is immunologically characterized by lymphocytic infiltration of the thyroid gland and the presence of thyroid-stimulating hormone (TSH) receptor antibodies (TSH-R-Ab), and is the most common autoimmune pathogenic cause of hyperthyroidism. Autoimmune thyroid dysfunction has been widely described in association with rheumatic diseases. A certain rate of coexistence of GD with LE, mainly SLE, has been reported in the literature. Herein, we present a rare case of Graves' hyperthyroidism complicated with DLE. Case Report:A 30-year-old female patient, with a history of hyperthyroidism and discontinued methimazole treatment, initially presented with symptoms of infection and oral ulcers. Thyroid hormone, thyroid-stimulating hormone receptor antibody, and immunological tests were consistent with a diagnosis of Graves' hyperthyroidism-associated DLE. Corticosteroids and radioactive iodine (RAI) were used to treat DLE and GD, respectively. Posttreatment evaluation suggested the remission of her hyperthyroidism and active DLE. Conclusions:Autoimmune thyroid diseases have been previously described in association with rheumatic diseases. This association shows the importance of prompt awareness of the increased risk of DLE when evaluating autoimmune thyroid dysfunction, especially under certain conditions, such as after treatment with anti-thyroid drugs (ATDs), or in the absence of multiple organ damage manifestations of SLE.

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Single-cell sequencing shows cellular heterogeneity of cutaneous lesions in lupus erythematosus

Cited by 32 publications

References 72 publications

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

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

Regulatory T cells in peripheral tissue tolerance and diseases

A 30-Year-Old Woman with a History of Autoimmune Hyperthyroidism Presenting with Fever and Oral Ulcers, Diagnosed with Discoid Lupus Erythematosus

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