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Elevated transferrin receptor impairs T cell metabolism and function in systemic lupus erythematosus.
Voss, Kelsey; Sewell, Allison E; Krystofiak, Evan S; Gibson-Corley, Katherine N; Young, Arissa C; Basham, Jacob H; Sugiura, Ayaka; Arner, Emily N; Beavers, William N; Kunkle, Dillon E; Dickson, Megan E; Needle, Gabriel A; Skaar, Eric P; Rathmell, W Kimryn; Ormseth, Michelle J; Major, Amy S; Rathmell, Jeffrey C.
Afiliación
  • Voss K; Division of Molecular Pathogenesis, Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Sewell AE; Division of Molecular Pathogenesis, Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Krystofiak ES; Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA.
  • Gibson-Corley KN; Division of Comparative Medicine, Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Young AC; Division of Molecular Pathogenesis, Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Basham JH; Division of Molecular Pathogenesis, Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Sugiura A; Division of Molecular Pathogenesis, Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Arner EN; Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Beavers WN; Division of Molecular Pathogenesis, Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Kunkle DE; Division of Molecular Pathogenesis, Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Dickson ME; Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Needle GA; Division of Rheumatology and Immunology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Skaar EP; Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Rathmell WK; Division of Molecular Pathogenesis, Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Ormseth MJ; Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Major AS; Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Rathmell JC; Vanderbilt Institute for Chemical Biology, Vanderbilt University, Nashville, TN, USA.
Sci Immunol ; 8(79): eabq0178, 2023 01 13.
Article en En | MEDLINE | ID: mdl-36638190
T cells in systemic lupus erythematosus (SLE) exhibit multiple metabolic abnormalities. Excess iron can impair mitochondria and may contribute to SLE. To gain insights into this potential role of iron in SLE, we performed a CRISPR screen of iron handling genes on T cells. Transferrin receptor (CD71) was identified as differentially critical for TH1 and inhibitory for induced regulatory T cells (iTregs). Activated T cells induced CD71 and iron uptake, which was exaggerated in SLE-prone T cells. Cell surface CD71 was enhanced in SLE-prone T cells by increased endosomal recycling. Blocking CD71 reduced intracellular iron and mTORC1 signaling, which inhibited TH1 and TH17 cells yet enhanced iTregs. In vivo treatment reduced kidney pathology and increased CD4 T cell production of IL-10 in SLE-prone mice. Disease severity correlated with CD71 expression on TH17 cells from patients with SLE, and blocking CD71 in vitro enhanced IL-10 secretion. T cell iron uptake via CD71 thus contributes to T cell dysfunction and can be targeted to limit SLE-associated pathology.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Transferrina / Linfocitos T Reguladores / Lupus Eritematoso Sistémico Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Sci Immunol Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Transferrina / Linfocitos T Reguladores / Lupus Eritematoso Sistémico Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Sci Immunol Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos