Stroke causes systemic immunosuppression. T lymphocytes are involved in infarct size in the early stages of stroke. However, the phenotypes of T lymphocytes and their functions in peripheral immune organs and the brain have not been well analyzed in the acute and chronic phases of stroke. Here, we investigated pathological phenotypic alterations in the systemic immune response, especially changes in T lymphocytes, from one day to six months after ischemic stroke in mice. Impairment in thymocyte numbers, development, proliferation, and apoptosis were observed for up to two weeks. The number of mature T cells in the spleen and blood decreased and showed reduced interferon-γ production. Increased numbers of CD4-CD8-CD3 + double-negative T cells were observed in the mouse brain during the early stages of stroke, whereas interleukin (IL)-10 + Foxp3 + regulatory T lymphocytes increased from two weeks during the chronic phase. These phenotypes correlated with body weight and neurological severity scores. The recovery of T lymphocyte numbers and increases in IL-10 + Foxp3 + regulatory T lymphocytes may be important for long-term neurological outcomes. Dynamic changes in T lymphocytes between the acute and chronic phases may play different roles in pathogenesis and recovery. This study provides fundamental information regarding the T lymphocyte alterations from the brain to the peripheral immune organs following stroke.

Atopic dermatitis (AD) is a chronic inflammatory skin disease. A hallmark of AD is dry itchy skin that results from defects in the epidermal barrier function. Aloe vera is used widely to promote general health and is administered topically to treat skin conditions such as eczema, burns and wounds. However, effects of A vera on AD were not fully elucidated. In this study, we investigated the oral administration of processed A vera gel (PAG) containing low molecular weight Aloe polysaccharides to treat ovalbumin (OVA)‐induced AD in mice. Oral administration of PAG suppressed total and OVA‐specific IgE production in sera and decreased the epidermal thickness of skin. Numbers of Ki‐67‐positive cells were reduced by PAG treatment. Expression levels of tight junction genes, including those that encode ZO‐1, Claudin‐1 and Claudin‐8, were decreased in AD skin lesions, whereas oral administration of PAG partially restored the expression levels of tight junction genes. In addition, IL‐4 and IL‐17A mRNA transcript levels were reduced in skin lesions after PAG treatment. Taken together, our findings suggest that oral administration of PAG ameliorated AD, normalized tight junction gene expression and suppressed inflammatory cytokines in AD skin.

BackgroundT lymphocytes are involved in infarct size at the early stage of stroke. However, the phenotypes of T lymphocytes and their functions in peripheral immune organs and the brain have not been well-analyzed from the acute to the chronic phase of stroke.MethodsA 45 min transient middle cerebral artery occlusion mouse model was used. The phenotypes of T lymphocytes in the thymus, spleen, blood, and brain were determined using the neurological severity score (NSS) and body weights during the 6-month follow-up. ResultsImpairment of thymocyte numbers, development, proliferation, and apoptosis was observed for up to 2 weeks. The number of mature T cells in the spleen and blood decreased and showed less interferon- production for up to 2 weeks. Increased numbers of CD44+CD62L- effector T cells and CD4-CD8-CD3+ double negative T cells were observed in mouse brains in the early phase of stroke, while interleukin (IL)-10+Foxp3+ regulatory T cell levels increased for 1 week during the chronic phase. These phenotypes were correlated with body weight and the NSS. ConclusionsThe recovery of T lymphocyte numbers and increased IL-10+Foxp3+ regulatory T lymphocytes may be important for the improvement of long-term neurological outcomes. Dynamic changes in T lymphocytes from the acute and chronic phase may play different roles, such as pathological and recovery roles, respectively. This study provides fundamental information regarding the T lymphocyte alterations from the brain to the peripheral immune organs from the acute to the chronic phase of stroke.

Aryl hydrocarbon receptor (AhR), a ligand-induced transcription factor, is known to be involved in the balance between inflammatory and suppressive/regulatory T cell activity. Mesenchymal stem cells (MSCs) possess immunomodulatory activities, including suppression of T- and B-cell activation. MSC-mediated immunosuppression occurs via nitric oxide (NO) in mice. Here, we isolated MSCs from Ahr−/− bone marrow in mice and found less immunosuppressive function compared to the wild type (WT)-MSCs. When MSCs are co-cultured with T cells in the presence of anti-CD3 and anti-CD28 antibodies, the AhR-deficient MSCs less inhibited T-cell proliferation, CD25 and CD122 expression and cytokine productions such as IFN-γ, IL-17A compared with wild type MSCs. In addition, we found AhR-deficient MSCs produce less inducible nitric oxide synthase (iNOS) and NO compared with wild type MSCs, when MSCs were stimulated with IFN-γ, TNF-α, and IL-1β. Since MSCs has been used for the treatment of graft-vs-host disease (GvHD), we injected the WT and AhR-deficient MSCs into the GvHD mice. The AhR-deficient MSCs showed less therapeutic efficacy compared to the WT MSCs. We think that the AhR is involved in the production of NO via regulating iNOS expression which is required for the therapeutic efficacy of MSCs.