Discovery of resident memory T cells in inflammatory vitiligo: A case report.

RATIONALE: The purpose of this report was to describe resident memory cluster of differentiation 8 (CD8) + T cells may contribute to the progression of inflammatory vitiligo. PATIENT CONCERNS: A 32-year-old male has a stable vitiligo for 1 year, then some patches present inflammatory erythema. Two years later, the inflammatory patches enlarged and joined together, and the remaining 2 common patches shows repigmentation and no change respectively. Both CD69 + CD8 + T cells and CD103 + CD8 + T cells showed marked increase in inflammatory vitiligo than common vitiligo. DIAGNOSIS: Histological findings show that the numbers of lymphocytes are increased in inflammatory vitiligo than common vitiligo. Immunofluorescence staining show that the numbers of CD69 + CD8 + T cells demonstrated a marked increase in inflammatory vitiligo than common vitiligo. INTERVENTIONS: Without any intervention. OUTCOMES: The previous upper 2 patches on the abdomen with erythematous rim were enlarged and joined together. However the lowest lesion with uninflamed common rim on the abdomen remained static, the one on the right groin showed spot-like repigmentation. LESSONS: This case report demonstrates that resident memory CD8 + T cells may contribute to the progression of inflammatory vitiligo.

Dynamics and asymptotic profiles of steady states of an SIRS epidemic model in spatially heterogenous environment.

This paper performs qualitative analysis on a reaction-diffusion SIRS epidemic system with ratio-dependent incidence rate in spatially heterogeneous environment. The threshold dynamics in the term of the basic reproduction number R0 is established. And the asymptotic profile of endemic equilibrium is determined if the diffusion rate of the susceptible individuals is small. The results show that restricting the movement of susceptible individuals can effectively control the number of infectious individuals.

Attenuation of peripheral regulatory T-cell suppression of skin-homing CD8⁺T cells in atopic dermatitis.

PURPOSE: Cutaneous lymphocyte-associated antigen (CLA)-expressing CD8⁺T cells have been known to play an important role in the pathogenesis of atopic dermatitis (AD). However, the mechanisms underlying the loss of self-tolerance remain unclear. Regulatory T cells (Tregs) play a key role in the development of homeostasis in the immune system. We, therefore, hypothesized that a reduced ability of Tregs to inhibit autologous CD8⁺CLA⁺T cells might be underlying mechanism in AD. MATERIALS AND METHODS: CD8⁺CLA⁺T cells and Tregs were obtained from the peripheral blood of AD patients and control volunteers. The frequencies of CD8⁺CLA⁺T cells were evaluated. The proliferative responses of CD8⁺CLA⁺T cells were assessed by flow cytometry, and the levels of transforming growth factor-ß1 (TGF-ß1) and interleukin-10 (IL-10) in culture supernatants were detected by enzyme-linked immunosorbent assay. RESULTS: Our results revealed higher frequency and increased expression of perforin and granzyme-B in peripheral CD8⁺CLA⁺T cells in AD, and lower inhibitory ability of Tregs on proliferation of CD8⁺CLA⁺T cells in AD. Meanwhile, the levels of TGF-ß1 produced by Tregs were significantly lower in AD, and anti-TGF-ß1 abolished such suppression. CONCLUSION: The attenuated inhibitory ability of Tregs on hyper-activated autologous CD8⁺CLA⁺T cells, mediated by TGF-ß1, plays an important role in the pathogenesis of AD.

Regulatory T cells from active non-segmental vitiligo exhibit lower suppressive ability on CD8+CLA+ T cells.

BACKGROUND: Recent studies have shown that vitiligo is a T-cell mediated autoimmune disease. Skin-homing cytotoxic T lymphocytes expressing cutaneous lymphocyte-associated antigen (CLA) have been suggested to be responsible for the destruction of melanocytes in vitiligo. An aberration in the suppressive function of regulatory T cells (Tregs) has been reported in vitiligo patients. However, whether the weakened suppressive ability of the Tregs contributes to hyper-activated skin homing CD8(+)CLA(+) T cells remains to be determined. OBJECTIVES: To investigate the inhibition of circulating Tregs on the proliferation of autologous CD8(+)CLA(+) T cells in non-segmental vitiligo patients. METHODS: CD8(+)CLA(+) T cells and Tregs were obtained from the peripheral blood of 13 non-segmental vitiligo patients and 7 controls. The proliferative responses of CD8(+)CLA(+) T cells were assessed in the absence or presence of autologous Tregs, and the levels of Transforming Growth Factor ß1(TGF-ß1) and IL-10 in culture supernatants were detected by enzyme-linked immunosorbent assay. RESULTS: The proliferative responses of circulating CD8(+)CLA(+) T cells in the presence of Tregs were significantly higher in the active vitiligo than in the stable vitiligo and control groups. Tregs from active vitiligo patients exhibited a lower inhibitory effect on proliferation of CD8(+)CLA(+) T cells. The levels of TGF-ß1 produced by Tregs were significantly lower in active vitiligo than other groups and anti-TGF-ß1 antibodies could abrogate the suppressive function of Tregs. CONCLUSIONS: The functional activity of Tregs is compromised in active vitiligo patients. TGF-ß1 plays an important role in the autoimmune mechanism of the disease.

Ginsenosides Rb1 and Rg1 Stimulate Melanogenesis in Human Epidermal Melanocytes via PKA/CREB/MITF Signaling.

Reduced or defective melanin skin pigmentation may cause many hypopigmentation disorders and increase the risk of damage to the skin triggered by UV irradiation. Ginsenosides Rb1 and Rg1 have many molecular targets including the cAMP-response element-binding protein (CREB), which is involved in melanogenesis. This study aimed to investigate the effects of ginsenosides Rb1 and Rg1 on melanogenesis in human melanocytes and their related mechanisms. The effects of Rb1 and Rg1 on cell viability, tyrosinase activity, cellular melanin content and protein levels of tyrosinase, microphthalmia-associated transcription factor (MITF), and activation of CREB in melanocytes were assessed. Results showed that Rb1 or Rg1 significantly increased cellular melanin content and tyrosinase activity in a dose-dependent manner. By contrast, the cell viability of melanocytes remained unchanged. After exposure to Rb1 or Rg1, the protein levels of tyrosinase, MITF, and phosphorylated CREB were significantly increased. Furthermore, pretreatment with the selective PKA inhibitor H-89 significantly blocked the Rb1- or Rg1-induced increase of melanin content. These findings indicated that Rb1 and Rg1 increased melanogenesis and tyrosinase activity in human melanocytes, which was associated with activation of PKA/CREB/MITF signaling. The effects and mechanisms of Rb1 or Rg1 on skin pigmentation deserve further study.

Characterization of circulating CD8+T cells expressing skin homing and cytotoxic molecules in active non-segmental vitiligo.

BACKGROUND: Vitiligo is caused by melanocyte depletion. Studies have suggested that skin-homing cytotoxic T lymphocytes that express cutaneous lymphocyte-associated antigen (CLA) are responsible for melanocyte depletion. The characteristics of these skin-homing cytotoxic T cells have not been well established yet. OBJECTIVES: To investigate the frequency of skin-homing CD8(+)T cells (CD8(+)CLA(+)T cells) and their expression of cytotoxic molecules, as well as migration-related molecules in CD8(+)T cell in non-segmental vitiligo patients. MATERIALS & METHODS: The frequency of CD8(+)CLA(+)T cells and their expression of cytotoxic molecules (perforin, granzyme-B and FasL) in peripheral blood of patients with non-segmental vitiligo were assessed using flow cytometry. Levels of chemokine receptors (CCR4, CCR10) on CD8(+)T cells were evaluated. RESULTS: Our results revealed a higher frequency and increased expression of perforin and granzyme-B in circulating CD8(+)CLA(+)T cells from patients with active vitiligo. The expression levels of CCR4 increased in CD8(+)T cells in active vitiligo patients. CONCLUSION: Patients with active non-segmental vitiligo have a higher frequency of CD8(+)CLA(+)T cells and hyper-activated cytotoxic functions, which may be involved in the pathogenesis of non-segmental vitiligo.