scholarly journals T cell receptor sequencing specifies psoriasis as a systemic and atopic dermatitis as a skin-focused, allergen-driven disease

2021 ◽  
Author(s):  
Lennart M Roesner ◽  
Ahmed K Farag ◽  
Rebecca Pospich ◽  
Stephan Traidl ◽  
Thomas Werfel
Keyword(s):  
T Cells ◽  
Atopic Dermatitis ◽  
T Cell ◽  
Mononuclear Cells ◽  
Skin Diseases ◽  
Developed Countries ◽  
Skin Lesions ◽  
Psoriatic Skin ◽  
Skin Homing ◽  
Circulating T Cells

Atopic dermatitis (AD) and psoriasis represent two of the most common inflammatory skin diseases in developed countries. A hallmark of both diseases is T cell infiltration into the skin. However, it is still not clarified to what extent these infiltrating T cells are antigen-specific skin-homing T cells or unspecific heterogeneous bystander cells. To elucidate this, T cells from lesional skin and from blood of 10 AD and 11 psoriasis patients were compared by receptor (TCR) sequencing. Therefore, peripheral blood mononuclear cells (PBMC) were cell-sorted according to expression of the cutaneous leukocyte antigen (CLA) into skin-homing (CLA+) and non-skin-homing (CLA-) subfractions. Aeroallergen-specific T cell lines were grown from AD patients' PBMC in parallel. Intra-individual comparison of TCRB CDR3 regions revealed that clonally expanded T cells in skin lesions of both AD and psoriasis patients corresponded to skin-homing circulating T cells. However, in psoriasis patients, these T cell clones were also detectable to a larger extent among CLA- circulating T cells. Up to 28% of infiltrating cells were identified as allergen-specific by overlapping TCR sequences. Our data shows that in line with the systemic nature of psoriasis, T cells infiltrating psoriatic skin lesions do not exclusively home to the skin and are therefore not specific to antigens that are exclusively encountered at the skin. T cells driving AD skin inflammation appear to home nearly exclusively to the skin and are, to a certain extent, specific to aeroallergens.

Fucosyltransferase VII-positive, skin-homing T cells in the blood and skin lesions of atopic dermatitis patients

2008 ◽  
Vol 17 (3) ◽  
pp. 170-176 ◽  
Author(s):  
Yoshiko Mizukawa ◽  
Ryo Takahashi ◽  
Yoshimi Yamazaki ◽  
Momoko Kimishima ◽  
Tetsuo Shiohara
Keyword(s):  
T Cells ◽  
Atopic Dermatitis ◽  
Skin Lesions ◽  
Positive Skin ◽  
Skin Homing

Association between T cell receptor variable segments, skin homing T cells and staphylococcal infection in atopic dermatitis

1997 ◽  
Vol 56 ◽  
pp. 436
Author(s):  
M.J. Torres ◽  
F.J. Gonzalez ◽  
J.L. Corzo ◽  
M.D. Giron ◽  
M.J. Carvajal ◽  
...  
Keyword(s):  
T Cells ◽  
Atopic Dermatitis ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Staphylococcal Infection ◽  
Skin Homing

scholarly journals Skin-derived interleukin-7 contributes to the proliferation of lymphocytes in cutaneous T-cell lymphoma

Blood ◽  
2006 ◽  
Vol 107 (6) ◽  
pp. 2440-2445 ◽  
Author(s):  
Kei-ichi Yamanaka ◽  
Rachael Clark ◽  
Benjamin Rich ◽  
Rebecca Dowgiert ◽  
Kazuki Hirahara ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Normal Skin ◽  
Neutralizing Antibody ◽  
Cell Receptor ◽  
Skin Lesions ◽  
Interleukin 7 ◽  
Receptor Repertoire ◽  
T Cell Lymphomas ◽  
Skin Homing

AbstractCutaneous T-cell lymphomas (CTCLs) are malignancies of T cells that have a special affinity for the skin. We have previously reported that much of the T-cell receptor repertoire is altered in CTCL, and both malignant and nonmalignant clones are numerically expanded, presumably in response to T-cell trophic cytokines. We therefore examined levels of the T-cell trophic cytokines IL-2, IL-4, IL-7, IL-12, IL-13, and IL-15 in plasma in 93 CTCL patients and healthy controls. Only IL-7 levels were elevated in CTCL. We next looked at lesional skin from patients with CTCL and found elevated levels of IL-7 mRNA. Explant cultures of normal and lesional CTCL skin biopsies revealed significantly more IL-7 protein production in CTCL skin. Additionally, cultures of CTCL skin released greater numbers of T cells than normal skin; this was blocked by the addition of an IL-7 neutralizing antibody. Finally, these cultures induced proliferation of normal peripheral skin-homing T cells that were added to the cultures. These observations led us to postulate that IL-7 produced by skin cells contributes to the survival and proliferation of T cells within skin lesions and is likely the source of elevated circulating IL-7 in CTCL. (Blood. 2006;107:2440-2445)

scholarly journals T lymphocytes in skin lesions of psoriasis and mycosis fungoides express B7-1: a ligand for CD28

Blood ◽  
1994 ◽  
Vol 83 (9) ◽  
pp. 2580-2586 ◽  
Author(s):  
BJ Nickoloff ◽  
FO Nestle ◽  
XG Zheng ◽  
LA Turka
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Mycosis Fungoides ◽  
Skin Diseases ◽  
Family Members ◽  
Chinese Hamster ◽  
Cell Receptor ◽  
Skin Lesions ◽  
Epidermal Keratinocytes

The activation of T cells requires two distinct signals. One signal involves interaction of the antigen-specific T-cell receptor with major histocompatibility complex molecules plus antigenic peptide; a second signal, which is antigen nonspecific, is the interaction of CD28 with its natural ligands B7–1 and B7–2/B70. CD28 is expressed on 80% of T cells, is upregulated after activation, and binds to B7 gene-family members, found on antigen-presenting cells. Because of our interest in the immunologic basis of benign and malignant T-cell-mediated disorders of the skin, we investigated the cellular distribution of CD28 and B7 family members in lesions of psoriasis and mycosis fungoides. By immunostaining cryostat sections of skin, CD28 was found to be expressed on virtually all lymphocytes in the epidermis and dermis of both skin diseases. Surprisingly, B7–1 was also found to be expressed on virtually all lymphocytes in the epidermis and dermis of both skin diseases. B7–1 expression was confirmed on CD3+ T lymphocytes using flow cytometry of single cell suspensions of fresh, unfixed psoriatic lesional tissue. To exclude the possibility that this result was caused by a second reagent contaminating the monoclonal antibody (MoAb) preparation, two different lots were used, and the MoAb was absorbed onto Chinese hamster ovary (CHO) transfectants expressing B7–1, or vector-only transfected CHO cells. These procedures confirmed that a B7- 1-like epitope was being recognized on psoriatic lesional T cells. In contrast to B7–1 expression on lymphocytes, B7–3, as defined by anti-BB- 1 MoAb reactivity, was found primarily on epidermal keratinocytes in both skin diseases and was not found on T cells. These results indicate that within two common skin disorders, lesional T cells accumulate in the dermis and epidermis, which express B7–1. Such expression may permit self-costimulation involving the CD28-mediated activation pathway, and thereby contribute to the ongoing T-cell proliferation present in these chronic, benign, and malignant skin diseases.

scholarly journals T lymphocytes in skin lesions of psoriasis and mycosis fungoides express B7-1: a ligand for CD28

Blood ◽  
1994 ◽  
Vol 83 (9) ◽  
pp. 2580-2586 ◽  
Author(s):  
BJ Nickoloff ◽  
FO Nestle ◽  
XG Zheng ◽  
LA Turka
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Lymphocytes ◽  
Mycosis Fungoides ◽  
Skin Diseases ◽  
Family Members ◽  
Chinese Hamster ◽  
Cell Receptor ◽  
Skin Lesions ◽  
Epidermal Keratinocytes

Abstract The activation of T cells requires two distinct signals. One signal involves interaction of the antigen-specific T-cell receptor with major histocompatibility complex molecules plus antigenic peptide; a second signal, which is antigen nonspecific, is the interaction of CD28 with its natural ligands B7–1 and B7–2/B70. CD28 is expressed on 80% of T cells, is upregulated after activation, and binds to B7 gene-family members, found on antigen-presenting cells. Because of our interest in the immunologic basis of benign and malignant T-cell-mediated disorders of the skin, we investigated the cellular distribution of CD28 and B7 family members in lesions of psoriasis and mycosis fungoides. By immunostaining cryostat sections of skin, CD28 was found to be expressed on virtually all lymphocytes in the epidermis and dermis of both skin diseases. Surprisingly, B7–1 was also found to be expressed on virtually all lymphocytes in the epidermis and dermis of both skin diseases. B7–1 expression was confirmed on CD3+ T lymphocytes using flow cytometry of single cell suspensions of fresh, unfixed psoriatic lesional tissue. To exclude the possibility that this result was caused by a second reagent contaminating the monoclonal antibody (MoAb) preparation, two different lots were used, and the MoAb was absorbed onto Chinese hamster ovary (CHO) transfectants expressing B7–1, or vector-only transfected CHO cells. These procedures confirmed that a B7- 1-like epitope was being recognized on psoriatic lesional T cells. In contrast to B7–1 expression on lymphocytes, B7–3, as defined by anti-BB- 1 MoAb reactivity, was found primarily on epidermal keratinocytes in both skin diseases and was not found on T cells. These results indicate that within two common skin disorders, lesional T cells accumulate in the dermis and epidermis, which express B7–1. Such expression may permit self-costimulation involving the CD28-mediated activation pathway, and thereby contribute to the ongoing T-cell proliferation present in these chronic, benign, and malignant skin diseases.

scholarly journals Attenuation of Peripheral Regulatory T-Cell Suppression of Skin-Homing CD8+T Cells in Atopic Dermatitis

2015 ◽  
Vol 56 (1) ◽  
pp. 196 ◽  
Author(s):  
Bao-Xiang Zhang ◽  
Jun-Cheng Lyu ◽  
Hai-Bo Liu ◽  
Dian-Qin Feng ◽  
Dian-Cai Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
Atopic Dermatitis ◽  
T Cell ◽  
Cd8 T Cells ◽  
Regulatory T Cell ◽  
T Cell Suppression ◽  
Skin Homing ◽  
Cell Suppression

scholarly journals Quantitative analysis of CD4+CD25+FoxP3+ regulatory T-cells in canine atopic dermatitis in Korea

2020 ◽  
Vol 65 (No. 6) ◽  
pp. 250-257
Author(s):  
DJ Lee ◽  
TH Chung ◽  
C Park
Keyword(s):  
T Cells ◽  
Atopic Dermatitis ◽  
Regulatory T Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Canine Atopic Dermatitis ◽  
Healthy Dogs ◽  
The Difference ◽  
Circulating T Cells

Recently, it was suggested that CD4<sup>+</sup>CD25<sup>+</sup>FoxP3<sup>+</sup> Tregs (Regulatory T-cells) exist in canine skin, although their numbers were not significantly different between healthy and atopic dogs. In this study, we investigated whether Treg frequencies correlate with the clinical features of canine atopic dermatitis (cAD). The goal of this study was to compare and analyse the numbers of the circulating Tregs in atopic and healthy dogs. In the peripheral blood mononuclear cells (PBMC) of healthy dogs, Tregs defined as CD4<sup>+</sup>CD25<sup>+</sup>FoxP3<sup>+</sup> Tregs in the peripheral blood ranged from 0.3% to 1.5%. By contrast, in atopic dogs, the same population ranged from 0.7% to 8.8%. The percentage of CD4<sup>+</sup>CD25<sup>+</sup>FoxP3<sup>+</sup> Tregs in gated CD4<sup>+</sup> T-cells was significantly higher in the peripheral blood of dogs with atopic dermatitis (n = 9) than in the healthy controls (n = 8). The difference in the Treg levels (CD4<sup>+</sup>CD25<sup>+</sup>FoxP3<sup>+</sup>) (P = 0.012) between the atopic and the healthy groups was statistically significant. The circulating T-cells (phenotype CD4<sup>+</sup>CD25<sup>+</sup>FoxP3<sup>+</sup> and CD4<sup>+</sup>FoxP3<sup>+</sup>) were increased significantly in the atopic dogs. The proportion of CD4<sup>+</sup>CD25<sup>+</sup>FoxP3<sup>+</sup> Tregs of the atopic dogs decreased with advancing age. These findings suggest that changes in the Tregs may mediate the pathogenesis of CAD.

Traditional Herbal Medicines, Newer Herbs and Other Novel Approaches Integrated in Herbal Medicine for Atopic Dermatitis-A Narrative Review

2020 ◽  
Vol 15 (3) ◽  
pp. 194-208
Author(s):  
Pravin Kumar ◽  
Dinesh Kumar Sharma ◽  
Mahendra Singh Ashawat
Keyword(s):  
Atopic Dermatitis ◽  
Herbal Medicines ◽  
Developed Countries ◽  
Skin Lesions ◽  
Scientific Data ◽  
Herbal Drugs ◽  
Biological Drugs ◽  
Alternative Treatment Option

Atopic Dermatitis (AD) is a prolonged reverting skin ailment with characteristically distributed skin lesions. In the previous decades, researchers had shown a marked interest in AD due to its increased prevalence in developed countries. Although different strategies including biological and immune modulators are available for the treatment of AD, each has certain limitations. The researchers had shown considerable interest in the management of AD with herbal medicines. The establishment of herbal drugs for AD might eliminate local as well as systemic adverse effects associated with long term use of corticosteroids and also higher cost of therapy with biological drugs. The present review discusses the traditional East Asian herbal medicines and scientific data related to newer herbal extracts or compositions for the treatment of AD. In vivo animal models and in vitro cell cultures, investigated with herbal medicines to establish a possible role in AD treatment, have also been discussed in the paper. The paper also highlights the role of certain new approaches, i.e. pharmacopuncture, a combination of allopathic and herbal medicines; and novel carriers (liposomes, cubosomes) for herbal drugs on atopic skin. In conclusion, herbal medicines can be a better and safe, complementary and alternative treatment option for AD.

scholarly journals Targeting CD38 is lethal to Breg-like chronic lymphocytic leukemia cells and Tregs, but restores CD8+ T-cell responses

2020 ◽  
Vol 4 (10) ◽  
pp. 2143-2157 ◽  
Author(s):  
Alak Manna ◽  
Timothy Kellett ◽  
Sonikpreet Aulakh ◽  
Laura J. Lewis-Tuffin ◽  
Navnita Dutta ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Cd8 T Cells ◽  
Mononuclear Cells ◽  
Transforming Growth Factor ◽  
Ex Vivo ◽  
Xenograft Model ◽  
Lymphocytic Leukemia ◽  
Dependent Manner

Abstract Patients with chronic lymphocytic leukemia (CLL) are characterized by monoclonal expansion of CD5+CD23+CD27+CD19+κ/λ+ B lymphocytes and are clinically noted to have profound immune suppression. In these patients, it has been recently shown that a subset of B cells possesses regulatory functions and secretes high levels of interleukin 10 (IL-10). Our investigation identified that CLL cells with a CD19+CD24+CD38hi immunophenotype (B regulatory cell [Breg]–like CLL cells) produce high amounts of IL-10 and transforming growth factor β (TGF-β) and are capable of transforming naive T helper cells into CD4+CD25+FoxP3+ T regulatory cells (Tregs) in an IL-10/TGF-β-dependent manner. A strong correlation between the percentage of CD38+ CLL cells and Tregs was observed. CD38hi Tregs comprised more than 50% of Tregs in peripheral blood mononuclear cells (PBMCs) in patients with CLL. Anti-CD38 targeting agents resulted in lethality of both Breg-like CLL and Treg cells via apoptosis. Ex vivo, use of anti-CD38 monoclonal antibody (mAb) therapy was associated with a reduction in IL-10 and CLL patient-derived Tregs, but an increase in interferon-γ and proliferation of cytotoxic CD8+ T cells with an activated phenotype, which showed an improved ability to lyse patient-autologous CLL cells. Finally, effects of anti-CD38 mAb therapy were validated in a CLL–patient-derived xenograft model in vivo, which showed decreased percentage of Bregs, Tregs, and PD1+CD38hiCD8+ T cells, but increased Th17 and CD8+ T cells (vs vehicle). Altogether, our results demonstrate that targeting CD38 in CLL can modulate the tumor microenvironment; skewing T-cell populations from an immunosuppressive to immune-reactive milieu, thus promoting immune reconstitution for enhanced anti-CLL response.

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