Antigen-driven bystander effect accelerates epicutaneous sensitization with a new protein allergen

Exposure to protein allergen epicutaneously, inducing a Th2-dominant immune response, sensitizes the host to the development of atopic disease. Antigen-driven bystander effect demonstrates that polarized T cells could instruct naïve T cells to differentiate into T cells with similar phenotype. In this study, we aimed to determine the contribution of antigen-driven bystander effect on epicutaneous sensitization with a newly introduced protein allergen. BALB/c mice were immunized intraperitoneally with BSA emulsified in alum, known to induce a Th2 response, three weeks before given BSA and OVA epicutaneously. Lymph node cells from these mice restimulated with OVA secreted higher levels IL-4, IL-5 and IL-13 as compared with cells from mice without BSA immunization. In addition, BALB/c mice immunized subcutaneously with BSA emulsified in complete Freund's adjuvant, known to induce a Th1-predominant response, also induced higher Th1 as well as Th2 cytokine response when restimulated with OVA as compared with mice without immunization. We demonstrated that subcutaneous immunization with BSA in CFA induced Th2 as well as Th1 response. The threshold of epicutaneous sensitization to OVA was also reduced, possibly due to increased expressions of IL-4 and IL-10 in the draining lymph nodes during the early phase of sensitization. In conclusion, antigen-driven bystander effect, whether it is of Th1- or Th2-predominant nature, can accelerate epicutaneous sensitization by a newly introduced protein allergen. These results provide a possible explanation for mono- to poly-sensitization spread commonly observed in atopic children

LOW-ENERGY VISIBLE LIGHT IRRADIATION MODULATES IMMUNE RESPONSES INDUCED BY EPICUTANEOUS SENSITIZATION WITH PROTEIN ANTIGEN

Epicutaneous sensitization has been an important route for protein allergen sensitization in atopic disease. Although the skin is irradiated by sunlight daily, the influence of visible light on epicutaneous sensitization has not been explored. In this study, by using a well-established murine protein-patch model, we show that low-energy visible light ( LEVL) irradiation could differentially modulate the predominant Th2 immune response induced by epicutaneous sensitization with protein antigen. When the induced Th2 response was strong, as usually observed in BALB/c mice, LEVL irradiation suppressed the response. In contrast, LEVL irradiation enhanced the weaker Th2 response in C57BL/6 mice . Increased IL-18 and decreased TGF-beta expression in draining lymph nodes after LEVL irradiation was observed in BALB/c mice, but not in C57BL/6 mice. LEVL irradiation also enhanced IL-18 expression in skin and reduced the downregulation of CD24 expression on epidermal Langerhans cells in draining lymph nodes of BALB/c mice. Collectively, these results provide evidence for immunomodulatory effects of LEVL irradiation and will help us develop a useful strategy for prevention of allergen sensitization

Clinicopathological features and prognosis of patients with de novo versus nevus-associated melanoma in Taiwan

<div><p>Studies surveying melanomas associated with melanocytic nevi in Asia are rare. In this study, we examined whether nevus-associated melanomas differ from de novo melanomas in terms of their associations with clinical factors, histologic characteristics, and patient survival in Taiwan. Using data on cancer cases obtained from the Department of Pathology archives and the Cancer Registry of National Taiwan University Hospital, we conducted a retrospective analysis of 103 consecutive melanoma patients who were diagnosed between 2010 and 2015 and received follow-up through November 2016. Approximately 17.5% of the melanomas in question were associated with a nevus. In patients under 65 years of age, non-acral lentiginous melanomas were significantly associated with a higher percentage of nevus-associated melanomas. The superficial spreading subtype, younger patient age, thinner tumor, intermittent solar exposure, and early stage were significant predictors of a melanoma being histologically associated with a nevus. The appearance of a nevus associated with a melanoma predicted better recurrence-free survival compared with de novo melanomas. Although acral lentiginous melanomas (70.9%) constituted the most common histologic subtype, only 9.6% of the acral lentiginous melanomas were associated with a nevus. Furthermore, there was no statistically significant difference between the nevus-associated and de novo acral lentiginous melanomas with regard to clinicopathological factors and survival. In conclusion, nevus-associated melanomas were uncommon among acral lentiginous melanomas. Relatedly, because over half of all melanomas in Asians are acral lentiginous melanomas, Asians are less likely than Caucasians to have nevus-associated melanomas.</p></div

Clinical and histologic characteristics.

<p>Clinical and histologic characteristics.</p

Clinical and histologic characteristics in acral lentigious melanomas.

<p>Clinical and histologic characteristics in acral lentigious melanomas.</p

Kaplan-Meier curves of survival for 73 patients with primary acral lentiginous melanomas.

<p>No overall (A), distant metastasis-free survival (B), and recurrence-free survival (C) differences were found between patients with de novo and nevus-associated acral lentiginous melanomas (<i>p</i> = 0.168, 0.159, and 0.091, respectively, log rank test).</p