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Copy number of the X-linked genes TLR7 and CD40L influences innate and adaptive immune responses.
Sarmiento, Luis; Svensson, Johan; Barchetta, Ilaria; Giwercman, Aleksander; Cilio, Corrado M.
Afiliação
  • Sarmiento L; Cellular Autoimmunity Unit, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden.
  • Svensson J; Department of Pediatrics, Skåne University Hospital, Lund University, Malmö, Sweden.
  • Barchetta I; Cellular Autoimmunity Unit, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden.
  • Giwercman A; Department of Experimental Medicine, Sapienza University, Rome, Italy.
  • Cilio CM; Molecular Reproductive Medicine, Department of Translational Medicine, Lund University, Skåne University Hospital, Malmö, Sweden.
Scand J Immunol ; 90(2): e12776, 2019 Aug.
Article em En | MEDLINE | ID: mdl-31069824
ABSTRACT
The number of the X chromosome-linked genes has been previously suggested to influence immune responses and the development of autoimmune diseases. In the present study, we aimed at evaluating the level of expression of CD40L (an X-linked gene involved in adaptive immunity) and TLR7 (an X-linked gene involved in innate immunity) in a variety of different karyotypes. Those included males, females and patients with X chromosome aneuploidy. Healthy females (46, XX; n = 10) and healthy males (46, XY; n = 10) were compared to females with Turner syndrome (TS) (45, X; n = 11) and males with Klinefelter syndrome (KS) (47, XXY; n = 5). Stimulation of peripheral blood mononuclear cells (PBMCs) with PMA and ionomycin resulted in higher percentage of CD3 + CD40L+ T cells (P < 0.001) and higher level expression of CD40L in T cell (P < 0.001) in female and KS patients compared with male and TS patients. TLR7-mediated IFN-alpha production by HLADR + CD3- CD19- cells was significantly upregulated in healthy women compared with healthy males, TS and KS patients (P < 0.001). TLR7 agonist-stimulated PBMCs from healthy females and KS patients expressed significantly higher levels of TLR7 mRNA than those from male and TS patients (P < 0.05). The increased expression of the X-linked genes TLR7 and CD40L in healthy females and KS patients suggests that the presence of two X chromosomes plays a major role in enhancing both innate and adaptive immune responses. These results may contribute to the explanation of sex-based differences in immune biology and the sex bias in predisposition to autoimmune diseases.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dosagem de Genes / Ligante de CD40 / Cromossomos Humanos X / Receptor 7 Toll-Like / Imunidade Adaptativa / Imunidade Inata Limite: Female / Humans / Male Idioma: En Revista: Scand J Immunol Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Suécia

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dosagem de Genes / Ligante de CD40 / Cromossomos Humanos X / Receptor 7 Toll-Like / Imunidade Adaptativa / Imunidade Inata Limite: Female / Humans / Male Idioma: En Revista: Scand J Immunol Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Suécia