Your browser doesn't support javascript.
loading
Anxiolytic Drug FGIN-1-27 Ameliorates Autoimmunity by Metabolic Reprogramming of Pathogenic Th17 Cells.
Singh, Anju; Dashnyam, Myagmarjav; Chim, Bryan; Escobar, Thelma M; Dulcey, Andrés E; Hu, Xin; Wilson, Kelli M; Koganti, Prasanthi P; Spinner, Camille A; Xu, Xin; Jadhav, Ajit; Southall, Noel; Marugan, Juan; Selvaraj, Vimal; Lazarevic, Vanja; Muljo, Stefan A; Ferrer, Marc.
Afiliação
  • Singh A; Division of Preclinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, Rockville, MD, USA.
  • Dashnyam M; Division of Preclinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, Rockville, MD, USA.
  • Chim B; Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA.
  • Escobar TM; Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA.
  • Dulcey AE; Division of Preclinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, Rockville, MD, USA.
  • Hu X; Division of Preclinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, Rockville, MD, USA.
  • Wilson KM; Division of Preclinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, Rockville, MD, USA.
  • Koganti PP; Department of Animal Science, College of Agriculture and Life Sciences, Cornell University, Ithaca, New York, USA.
  • Spinner CA; Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Xu X; Division of Preclinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, Rockville, MD, USA.
  • Jadhav A; Division of Preclinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, Rockville, MD, USA.
  • Southall N; Division of Preclinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, Rockville, MD, USA.
  • Marugan J; Division of Preclinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, Rockville, MD, USA.
  • Selvaraj V; Department of Animal Science, College of Agriculture and Life Sciences, Cornell University, Ithaca, New York, USA.
  • Lazarevic V; Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. vanja.lazarevic@nih.gov.
  • Muljo SA; Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA. stefan.muljo@nih.gov.
  • Ferrer M; Division of Preclinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, Rockville, MD, USA. marc.ferrer@nih.gov.
Sci Rep ; 10(1): 3766, 2020 02 28.
Article em En | MEDLINE | ID: mdl-32111885
ABSTRACT
Th17 cells are critical drivers of autoimmune diseases and immunopathology. There is an unmet need to develop therapies targeting pathogenic Th17 cells for the treatment of autoimmune disorders. Here, we report that anxiolytic FGIN-1-27 inhibits differentiation and pathogenicity of Th17 cells in vitro and in vivo using the experimental autoimmune encephalomyelitis (EAE) model of Th17 cell-driven pathology. Remarkably, we found that the effects of FGIN-1-27 were independent of translocator protein (TSPO), the reported target for this small molecule, and instead were driven by a metabolic switch in Th17 cells that led to the induction of the amino acid starvation response and altered cellular fatty acid composition. Our findings suggest that the small molecule FGIN-1-27 can be re-purposed to relieve autoimmunity by metabolic reprogramming of pathogenic Th17 cells.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ansiolíticos / Autoimunidade / Encefalomielite Autoimune Experimental / Células Th17 / Técnicas de Reprogramação Celular / Ácidos Indolacéticos Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Sci Rep Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ansiolíticos / Autoimunidade / Encefalomielite Autoimune Experimental / Células Th17 / Técnicas de Reprogramação Celular / Ácidos Indolacéticos Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Sci Rep Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos