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The X-linked epigenetic regulator UTX controls NK cell-intrinsic sex differences.
Cheng, Mandy I; Li, Joey H; Riggan, Luke; Chen, Bryan; Tafti, Rana Yakhshi; Chin, Scott; Ma, Feiyang; Pellegrini, Matteo; Hrncir, Haley; Arnold, Arthur P; O'Sullivan, Timothy E; Su, Maureen A.
Afiliación
  • Cheng MI; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
  • Li JH; Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA, USA.
  • Riggan L; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
  • Chen B; Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA, USA.
  • Tafti RY; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
  • Chin S; Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA, USA.
  • Ma F; Department of Molecular, Cell, and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA.
  • Pellegrini M; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
  • Hrncir H; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
  • Arnold AP; Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA, USA.
  • O'Sullivan TE; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
  • Su MA; Department of Molecular, Cell, and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA.
Nat Immunol ; 24(5): 780-791, 2023 05.
Article en En | MEDLINE | ID: mdl-36928413
Viral infection outcomes are sex biased, with males generally more susceptible than females. Paradoxically, the numbers of antiviral natural killer (NK) cells are increased in males. We demonstrate that while numbers of NK cells are increased in male mice, they display decreased effector function compared to females in mice and humans. These differences were not solely dependent on gonadal hormones, because they persisted in gonadectomized mice. Kdm6a (which encodes the protein UTX), an epigenetic regulator that escapes X inactivation, was lower in male NK cells, while NK cell-intrinsic UTX deficiency in female mice increased NK cell numbers and reduced effector responses. Furthermore, mice with NK cell-intrinsic UTX deficiency showed increased lethality to mouse cytomegalovirus. Integrative multi-omics analysis revealed a critical role for UTX in regulating chromatin accessibility and gene expression critical for NK cell homeostasis and effector function. Collectively, these data implicate UTX as a critical molecular determinant of sex differences in NK cells.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Caracteres Sexuales / Genes Ligados a X Límite: Animals / Female / Humans / Male Idioma: En Revista: Nat Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA 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: Caracteres Sexuales / Genes Ligados a X Límite: Animals / Female / Humans / Male Idioma: En Revista: Nat Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos