RESUMO
Treg cells are not only crucial for controlling immune responses to autoantigens but also prevent those directed towards commensal pathogens. Control of effector immune responses by Treg cells depend on their capacity to accumulate at inflammatory site and accordingly accommodate to inflammatory environment. Till date, the factors associated with maintaining these aspects of Treg phenotype is not understood properly. Here we have shown that a known nuclear matrix binding protein SMAR1 is selectively expressed more in colonic Treg cells and is required for their ability to accumulate at inflammatory site and to sustain high levels of Foxp3 and IL-10 expression during acute colitis. Elimination of anti-inflammatory subsets revealed a protective role for IL-10 producing Treg cells in SMAR1(-/-) mice. Moreover, a combined action of Foxp3 and SMAR1 restricts effector cytokine production and enhance the production of IL-10 by colonic Treg cells that controls acute colitis. This data highlights a critical role of SMAR1 in maintaining Treg physiology during inflammatory disorders.
Assuntos
Proteínas de Ciclo Celular/fisiologia , Colite/imunologia , Proteínas de Ligação a DNA/fisiologia , Interleucina-10/fisiologia , Proteínas Nucleares/fisiologia , Linfócitos T Reguladores/imunologia , Doença Aguda , Animais , Proteínas de Ciclo Celular/genética , Diferenciação Celular , Proteínas de Ligação a DNA/genética , Camundongos , Camundongos Knockout , Proteínas Nucleares/genética , Linfócitos T Reguladores/patologiaRESUMO
Cutaneous leishmaniasis affects nearly 0.7 to 1.3 million people annually. Treatment of this disease is difficult due to lack of appropriate medication and the growing problem of drug resistance. Natural compounds such as coumarins serve as complementary therapeutic agents in addition to the current treatment modalities. In this study, we have performed an in-silico screening of the coumarin derivatives and their anti-leishmanial properties has been explored both in-vitro and in-vivo. One of the compounds (compound 2) exhibited leishmanicidal activity and to further study its properties, nanoliposomal formulation of the compound was developed. Treatment of cutaneous lesions in BALB/c mice with compound 2 showed significantly reduced lesion size as compared to the untreated mice (p<0.05) suggesting that compound 2 may possess anti-leishmanial properties.