Thymus and activation-regulated chemokine in atopic dermatitis: Serum thymus and activation-regulated chemokine level is closely related with disease activity (original) (raw)
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Journal of Allergy and Clinical Immunology, 2002
Objective: The purpose of this study was to demonstrate the presence of thymus and activation-regulated chemokine (TARC) in platelets and its release during clotting and to evaluate the circulating levels of TARC, macrophage-derived chemokine (MDC), and eotaxin in control subjects and patients with AD. Methods: We compared plasma and serum contents of TARC, MDC, and eotaxin. We measured TARC contents in platelet lysates. We analyzed the correlation of plasma levels of TARC, MDC, and eotaxin with various clinicolaboratory parameters in patients with AD. Results: Serum contents of TARC rapidly increased during clot-ting, whereas those of MDC and eotaxin increased only slightly. We demonstrated that platelets contained TARC, and its levels were dramatically elevated in patients with AD. Platelets also released TARC on stimulation with thrombin. We therefore evaluated circulating levels of these chemokines in control subjects and patients with AD by using plasma samples. Plasma TARC levels were significantly increased in patients with AD (P < .0001) and showed significant correlations with severity scoring of atopic dermatitis (SCORAD) index (r = 0.665, P < .00001), serum lactate dehydrogenese levels (r = 0.696, P = .00001), eosinophil counts (r = 0.381, P = .007), and platelet counts (r = 0.562, P < .0001). Similarly, plasma MDC levels were significantly increased in patients with AD (P < .0001) and showed significant correlations with SCORAD index (r = 0.727, P < .0001), serum lactate dehydrogenese levels (r = 0.861, P < .0001), eosinophil counts (r = 0.505, P = .005), and platelet counts (r = 0.370, P = .01). On treatment, plasma TARC and MDC levels were dramatically decreased in accordance with improved SCORAD scores (P = .0012 and P = .0007, respectively). On the other hand, plasma eotaxin levels did not show any significant increase or correlation with any of the clinical parameters in patients with AD. Conclusion: Platelets from patients with AD contain high levels of TARC. Thus platelets might play an important role in AD pathogenesis by releasing T H 2-attracting TARC on activation. Furthermore, circulating levels of TARC and MDC, but not those of eotaxin, correlate well with the disease activity of AD. (J Allergy Clin Immunol 2002;110:139-46.)
Journal of Investigative Dermatology, 2000
Atopic dermatitis is an in¯ammatory skin disease in which the in¯ammation is characterized by the in¯ux of lymphocytes into the dermis. It is generally believed that atopic dermatitis is a Th 2 -type disease, i.e., the T lymphocytes produce interleukin-4, interleukin-5, interleukin-10, and interleukin-13, although it has become evident in recent years that the cytokine pro®le in the skin changes during the course of the disease towards a Th 1 -Th 2 mixed cytokine pro®le (interferon-g, tumor necrosis factor a, and interleukin-2). The lymphocytes that home into the skin express cutaneous lymphocyte-associated antigen, and it has recently been shown that most of the lymphocytes in this population express the chemokine receptor CCR4. CCR4 is the receptor for the CC chemokine TARC (thymus and activation regulated chemokine), and this chemokine is expressed predominantly by keratinocytes in the basal layer of the epidermis of lesional atopic dermatitis skin in mice. In humans, however, it was shown to be expressed in the endothelial cells of the dermis. We have examined the peripheral blood mononuclear cells of ato-pic dermatitis patients for the expression of cutaneous lymphocyte-associated antigen and CCR4 and compared them with peripheral blood mononuclear cells from normal controls. We found that the proportion of CLA + CCR4 + lymphocytes is upregulated in atopic dermatitis patients. In addition we have examined skin biopsies of lesional and nonlesional skin from atopic dermatitis patients and found that the keratinocytes, but not the endothelial cells, produce TARC in the lesional but not in the nonlesional skin. To gain insight in the stimulatory mechanisms for TARC production in keratinocytes, as previously observed in mice, we cultured HaCaT cells and found that interferon-g and tumor necrosis factor a work synergistically to induce TARC production. These observations suggest that the induction of TARC production in keratinocytes plays an important role in the late phase skin invasion by CCR4 + CLA + Th 2 -type lymphocytes in atopic dermatitis.
Journal of Investigative Dermatology, 1999
A subgroup of patients with atopic dermatitis are known to have normal serum total immunoglobulin E levels, undetectable specific immunoglobulin E, and negative skin prick tests towards allergens. This form of the disease has been termed nonallergic atopic dermatitis. In this study, we found that, among 1151 chronic atopic dermatitis patients, about 10% had normal serum immunoglobulin E levels with no evidence for immunoglobulin E sensitization. We investigated immunologic mechanisms of patients with ''allergic'' and ''nonallergic'' atopic dermatitis using peripheral blood and skin biopsy samples. Our data suggest that T cells are likely involved in the pathogenesis of both forms of atopic dermatitis. Skin T cells equally responded to superantigen, staphylococcal enterotoxin B, and produced interleukin-2, interleukin-5, interleukin-13, and interferon-γ in both forms of the disease. Interleukin-4, however, was not detectable in the skin biopsies of both atopic dermatitis A topic dermatitis (AD) is a chronic relapsing inflammatory skin disease characterized by typically distributed eczematous skin lesions with lichenification, pruritic excoriations, severely dry skin, and a susceptibility to cutaneous infections . Several lines of evidence suggest the contribution of immunologic mechanisms in the pathogenesis of AD. The skin lesions of AD patients are infiltrated by activated T cells, eosinophils, and antigen-presenting Langerhans cells that bind and present immunoglobulin (Ig) Ecomplexed allergens on their surface . In addition, activation of peripheral blood T cells that preferentially secrete T helper (Th) 2 cytokines and help B cells to produce large amounts of immunoglobulin (Ig) E has previously been reported to be associated with this skin disease (Walker et al,
Journal of Allergy and Clinical Immunology, 2003
Background: Both atopic dermatitis (AD) and psoriasis vulgaris (PsV) are characterized as chronic and relapsing inflammatory skin diseases associated with various immunologic abnormalities. Cutaneous T cell-attracting chemokine (CTACK; CCL27) is a member of the CC chemokine family and a functional ligand for CC chemokine receptor 10. It is selectively expressed in skin and attracts CC chemokine receptor 10-expressing skin-homing memory T cells. The epidermal keratinocyte is a main source of CTACK, suggesting the involvement of various inflammatory skin diseases. Objective: The purpose of this investigation was to clarify whether CTACK produced by keratinocytes is detected in the sera of patients with AD and PsV and to examine the correlation between the serum CTACK levels and disease activity of patients with AD and PsV. Methods: We measured the serum CTACK levels in 50 patients with AD, 30 patients with PsV, and 22 healthy control subjects. We also divided 50 patients with AD into 3 groups (ie, those with mild, moderate, and severe disease) and compared them among 3 categories. Moreover, we compared the serum CTACK levels of patients with AD and PsV with clinical or laboratory data. Immunohistochemical staining of CTACK and IFN-induced protein of 10 kd (IP-10; CXCL10) was performed on the lesional skin of patients with AD and PsV. Results: The serum CTACK levels in patients with AD and PsV were significantly higher than those in healthy control subjects. The serum CTACK levels in patients with AD significantly correlated with scoring atopic dermatitis (SCORAD) scores, serum soluble IL-2 receptor levels, serum soluble Eselectin levels, serum thymus and activation-regulated chemokine levels, and serum macrophage-derived chemokine levels. Serum CTACK levels in patients with PsV significantly correlated with the serum IP-10 levels but not with the Psoriasis Area and Severity Index score. Immunohistochemical stain-ing showed CTACK was strongly expressed in lesional keratinocytes of patients with AD and PsV, whereas IP-10 was strongly expressed in lesional keratinocytes of patients with PsV and focally in those with AD. Conclusion: These results suggest that CTACK might be one of the important chemokines for the pathogenesis of AD and PsV. (J Allergy Clin Immunol 2003;111:592-7.)
Journal of Dermatology, 2018
The T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is a co-inhibitory receptor mainly expressed on T cells. Although TIGIT plays an important role in various autoimmune diseases, its role in atopic dermatitis (AD) remains unclear. In this study, we examined the expression levels of TIGIT and their association with clinical features in patients with AD. TIGIT expression on CD4 + T cells, central memory T cells, effector memory T cells and regulatory T cells was determined by flow cytometry. CD4 + T cells exhibited enhanced TIGIT expression in patients with AD compared with healthy individuals. In particular, effector memory T cells and regulatory T cells, but not central memory T cells, exhibited higher TIGIT expression in patients with AD than in healthy individuals. The frequency of TIGIT + cells among CD4 + T cells was significantly increased in patients with mild AD compared with healthy individuals, while decreased in patients with severe AD. Consistently, the frequency of TIGIT + cells among CD4 + T cells was negatively correlated with both serum thymus and activation-regulated chemokine levels and immunoglobulin E levels in patients with AD. Furthermore, TIGIT expression on CD4 + T cells inhibited cell proliferation in patients with AD. These results suggest that TIGIT expression on CD4 + T cells in patients with AD may be increased to suppress chronic cutaneous inflammation. Moreover, TIGIT expression may be impaired in a subset of patients with AD, leading to a deterioration of skin inflammation. Our study may provide new insight into a TIGIT pathway-based therapeutic approach for AD.
TARC augments TNF-alpha-induced CTACK production in keratinocytes
Experimental Dermatology, 2004
Thymus-and activation-regulated chemokine (TARC)/CCL17 and cutaneous T cell-attracting chemokine (CTACK)/CCL27 are both pivotal mediators of the inflammatory reaction of atopic dermatitis (AD). TARC attracts CCR4 positive T cells known to be mainly of Th 2 subtype whereas CTACK attracts skin-homing T cells of both Th 1 and Th 2 subtype that express CCR10. We found that CTACK can be induced in cultured human keratinocytes by tumor necrosis factor-a (TNF-a), but not by TARC alone. However, if the keratinocytes were preincubated with TNF-a for 6 h, TARC was able to augment the CTACK-inducing effect of TNF-a. Performing immunohistochemical stainings, reversetranscription polymerase chain reaction (RT-PCR), and Western blotting, we found that TNF-a-induced CCR4 mRNA production, but that stimulated as well as non-stimulated keratinocytes expressed CCR4. In order to see if these results had any clinical relevance, we investigated the plasma concentrations of TARC and CTACK from 48 patients suffering from AD. This revealed that TARC and CTACK concentrations in plasma correlate with each other. Surprisingly, p-CTACK correlated inversely with SCORAD scores of the patients, which most likely is due to the treatment the patients received. Our results suggest that the primary Th 2-dominated inflammatory reaction in AD induced by TARC leads to an augmented skin-specific inflammatory reaction through CTACK.
Clinical <html_ent glyph="@amp;" ascii="&"/> Experimental Allergy, 2004
Background Atopic dermatitis (AD) is an inflammatory skin disease whose lesions can have two stages: acute and chronic. In skin biopsies a biphasic pattern of cytokine expression has been shown, Th2 in acute lesions and Th1 in chronic AD lesions. Objective We investigated the expression of an activation marker and a homing receptor, as well as cytokine production, in different peripheral blood T cell subpopulations from AD patients with chronic (Group A) and acute lesions (Group B) and controls. Methods We evaluated 26 adult AD patients (12 Group A, 14 Group B) and 14 non-atopic controls. IgE was measured by immunoassay. CD4, CD8, cutaneous-lymphocyte-associated antigen (CLA) and human leucocyte antigen (HLA)-DR expression, and cytokine production (IL-2, IL-13, IFN-g, TNF-a, IL-10, IL-4) were analysed in mononuclear cells by flow cytometry. Results In Group B there was a significant increase in eosinophil levels and a non-significant increase in IgE. In Group A we found an increase in CLA 1 CD4 1 cells (8.19 AE 1.84) compared with controls (4.83 AE 0.53) (Po0.05) and CD4 1 HLA-DR 1 cells in the CLA 1 subpopulation (45.54 AE 15.40) compared with controls (30.49 AE 6.07) (Po0.05). In the CLA 1 CD4 1 subpopulation, there was a significant increase in IL-4, IL-13 and TNF-a production in Group B (12.46 AE 7.7, 11.26 AE 5.97, 43.92 AE 15.55) compared with controls (5.34 AE 3.50, 4.54 AE 1.78, 19.29 AE 9.97) with no differences in Group A. Conclusion Greater immunological differences were detected in peripheral blood from patients with acute compared with chronic lesions, especially in the circulating T cell-subset with skin tropism that preferentially responded to cutaneous allergens. This is the first demonstration of phenotypic changes in circulating CLA 1 T cells between AD patients with acute and chronic lesions.
Cytokines and T cells in atopic dermatitis
European cytokine network, 2013
Atopic dermatitis (AD) is an inflammatory disorder of the skin characterized by an impaired immune response. Several effector T cell subsets, such as pro-inflammatory cells like Th9, Th17 and Th22 cells, expressing high levels of IL-9, IL-17 and IL-22, together with the anti-inflammatory, immuno-modulating Treg cells constitutively producing IL-10, seem to play a role in this condition. IL-9 and IL-9 receptors are significantly increased in lesional AD skin compared to normal control skin. In addition, some polymorphisms in IL-9 and IL-9r genes have been associated with AD. The role of IL-17 and IL-17-producing T cells remains under debate and conflicting data are available. IL-22-producing T-cells seem to correlate with the severity of the AD. The number and function of Treg cells, producing IL-10, have been widely investigated in AD with conflicting results. Other studies suggest that high levels of IL-31 or low levels of IL-21 might be involved in the pathogenesis of AD. This rev...