Search

It has been suggested that macrophages or inflammatory monocytes participate in the pathology of noise-induced hearing loss (NIHL), but it is unclear how extensively these cells contribute to the development of temporary and/or permanent NIHL. To address this question, we used clodronate liposomes to deplete macrophages and monocytes. After clodronate liposome injection, mice were exposed to 4-kHz octave band noise at 121 dB for 4 h. Compared to vehicle-injected controls, clodronate-treated mice exhibited significantly reduced permanent threshold shifts at 4 and 8 kHz and significantly smaller outer hair cell losses in the lower-apical cochlear turn. Following noise exposure, the stria vascularis had significantly more cells expressing the macrophage-specific protein F4/80, and this effect was significantly suppressed by clodronate treatment. These F4/80-positive cells expressed interleukin 1 beta (IL-1β), which noise exposure activated. However, IL-1β deficient mice did not exhibit significant resistance to intense noise when compared to wild-type mice. These findings suggest that macrophages that enter the cochlea after noise exposure are involved in NIHL, whereas IL-1β inhibition does not reverse this cochlear damage. Therefore, macrophages may be a promising therapeutic target in human sensorineural hearing losses such as NIHL. [ABSTRACT FROM AUTHOR]

IL-10-producing regulatory T cells (IL-10-producing Tregs) are one of the regulatory T cell subsets characterized by the production of high amounts of IL-10, the lack of FOXP3 expression and the strong immunosuppressive capabilities. IL-10-producing Tregs have been primarily reported as induced populations thus far, in part because identifying naturally occurring IL-10-producing Tregs was difficult due to the lack of definitive surface markers. Lymphocyte-activation gene 3 (LAG3) is a CD4 homologue that we have identified as being expressed on IL-10 producing Tregs. In human PBMC, LAG3 combined with CD49b efficiently identifies IL-10-producing Tregs. However, naturally occurring IL-10-producing Tregs in human secondary lymphoid tissue have not been described. In this report, we identified CD4 + CD25 − LAG3 + T cells in human tonsil. This T cell subset produced high amounts of IL-10 and expressed low levels of FOXP3. Surface markers and microarray analysis revealed that this is a distinct tonsillar CD4 + T cell subset. CD4 + CD25 − LAG3 + T cells expressed interleukin 10 (IL10), PR/SET domain 1 (PRDM1), and CD274 at high levels and chemokine receptor 5 (CXCR5) at low levels. CD4 + CD25 − LAG3 + T cells suppressed antibody production more efficiently than CD4 + CD25 + T cells, and CD4 + CD25 − LAG3 + T cells induced B cell apoptosis. Moreover, analysis of humanized mice revealed that this cell subset suppressed a graft-versus-host disease (GVHD) reaction in vivo . Our study reveals the existence of naturally occurring IL-10-producing Tregs in human secondary lymphoid tissue and their function in immune regulation. [ABSTRACT FROM AUTHOR]

Abstract: Phylogenetic analyses were performed for the taxonomically complicated group, Asarum sect. Asiasarum, using internal transcribed spacers (ITS) of nuclear ribosomal DNA. Direct sequences for 99 samples of a total of 14 taxa and geographic races and cloning analyses for 32 of these samples provided new insights that extensive reticulate evolution has occurred in this group. Eight taxa had slight or no polymorphism of the ITS sequences. On the other hand, the other five taxa had polymorphic ITS sequences composed of two ribotypes that were completely the same or almost the same as the sequences recognized in the taxa with only slight or no polymorphism, and were probably of diploid hybrid origin and to have retained their parental ribotypes. In terms of biogeographic implications, at least four interactions including migration, hybridization, and introgression, were presumed between the Japanese Archipelago and the continents, two times via a southern route, from the Korean Peninsula, and two times via a northern route, from Sakhalin or directly from the Eurasian continent. [Copyright &y& Elsevier]