Ultraviolet B-Induced Maturation of CD11b-Type Langerin- Dendritic Cells Controls the Expansion of Foxp3+ Regulatory T Cells in the Skin.

Skin dendritic cells (DCs) are divided into several subsets with distinctive functions. This study shows a previously unappreciated role of dermal CD11b-type Langerin- DCs in maintaining immunological self-tolerance after UVB exposure. After UVB exposure, dermal CD11b-type Langerin- DCs upregulated surface CD86 expression, induced proliferation of Foxp3+ regulatory T (Treg) cells without exogenous Ags, and upregulated a set of genes associated with immunological tolerance. This Treg-expansion activity was significantly hampered by CD80/CD86 blockade in vivo. These results indicate that CD11b-type Langerin- DCs from the UVB-exposed skin are specialized to expand Treg cells in the skin, which suppress autoimmunity.

Homeostasis of thymus-derived Foxp3+ regulatory T cells is controlled by ultraviolet B exposure in the skin.

Accumulating evidence shows that immunological tolerance induced by Ag administration together with UVB irradiation is dependent on Foxp3(+) CD4(+) regulatory T (Treg) cells. However, the mechanisms by which UVB controls Treg cells in the skin are currently unclear. In this study, we have shown that exposure to UVB induced expansion of Treg cells up to 50-60% of the CD4(+) T cells in the irradiated skin. The Treg cell expansion in the skin lasted for 2 wk after exposure, which contributed to homeostasis of Treg cells in the periphery later. UVB-expanded Treg cells formed clusters with dendritic cells and proliferated in situ. Furthermore, the expanded Treg cells appeared to derive from neuropilin 1(+) thymus-derived Treg (tTreg) cells in the periphery because UVB-expanded Treg cells possessed Treg cell-specific CpG hypomethylation pattern, as seen in tTreg cells. These results collectively indicate that homeostasis of tTreg cells is controlled by UVB exposure in the skin. UVB therapy may be useful for not only inflammatory skin disorders, but also autoimmunity, transplantation, and allergy.

Epidemiology of latent tuberculosis infection in Japan-born and foreign-born children in Japan.

Objective: This study aims to compare the epidemiology of notifications of latent tuberculosis infection (LTBI) among Japan-born and foreign-born children in Japan between 2010 and 2020, and to assess the language used during LTBI case interviews with parents or caregivers of foreign-born children with LTBI during 2019. Methods: Our study consisted of two parts: (1) an analysis of national data from the Japan Tuberculosis Surveillance (JTBS) system on the epidemiology of LTBI among Japan-born and foreign-born children in Japan, and (2) a survey of staff at public health centres that had registered at least one foreign-born child aged ≤ 14 years with LTBI. Data were extracted from the JTBS system for all children aged ≤ 14 years who were newly notified as having LTBI between 2010 and 2020, and analysed to determine trends, characteristics and treatment outcomes. Staff at relevant public health centres completed a self-administered survey. Results: A total of 7160 Japan-born and 320 foreign-born children were notified as having LTBI between 2010 and 2020. Compared with Japan-born children, foreign-born children notified as having LTBI were more likely to be older, have their mother or sibling as their source of infection and have LTBI detected via a routine school health check. At case interviews, the use of language interpretation services was limited, even when both parents were non-Japanese. No interview was directly conducted with children themselves, not even with school-aged children. Discussion: Foreign-born children and their parents may be unfamiliar with the system of testing for TB infection and the diagnosis of LTBI in Japan in school settings. Public health centres are required to provide education to patients and their families and care that takes into account cultural and linguistic differences. However, the provision of language support during case interviews may need strengthening.

Bath-PUVA therapy improves impaired resting regulatory T cells and increases activated regulatory T cells in psoriasis.

BACKGROUND: Bath-psoralen plus ultraviolet light A (PUVA) therapy is an effective, safe, and inexpensive treatment for psoriasis. Psoriasis might be due to an unbalanced ratio of Th17 cells and regulatory T cells (Treg). The Treg functional ratio is significantly lower in patients with psoriasis compared with controls and is inversely correlated with the Psoriasis Area and Severity Index score. We previously reported that bath-PUVA therapy significantly increases the number of Treg and restores Treg function to almost normal in most patients with psoriasis. OBJECTIVES: We examined the effects of bath-PUVA therapy on three distinct Foxp3+ subsets: activated Treg (aTreg), resting Treg (rTreg), and cytokine-secreting non-suppressive T cells. METHODS: We enrolled 15 patients with psoriasis and 11 healthy controls. We examined aTreg, rTreg, and cytokine-secreting non-suppressive T cells in peripheral blood obtained from the psoriasis patients before and after every fifth bath-PUVA therapy session. RESULTS: Levels of aTreg, which are considered to have the strongest suppressive activity in patients with psoriasis, were significantly increased in the early bath-PUVA therapy sessions, and then diminished. Levels of rTreg were lower in psoriasis patients than in healthy controls, and increased during bath-PUVA therapy. CONCLUSIONS: Bath-PUVA therapy induced aTreg and rTreg concomitantly with an improvement in the psoriatic lesions, suggesting a mechanism for the effectiveness of bath-PUVA therapy for psoriasis patients.