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Copy number of the X-linked genes TLR7 and CD40L influences innate and adaptive immune responses

Sarmiento, Luis LU ; Svensson, Johan LU ; Barchetta, Ilaria LU ; Giwercman, Aleksander LU and Cilio, Corrado M. LU (2019) In Scandinavian Journal of Immunology
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... (More)

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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author
organization
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Contribution to journal
publication status
epub
subject
keywords
autoimmunity, blood, human, T cells
in
Scandinavian Journal of Immunology
publisher
Wiley-Blackwell
external identifiers
  • scopus:85067864584
ISSN
0300-9475
DOI
10.1111/sji.12776
language
English
LU publication?
yes
id
3ff277a5-2dc1-48ef-8033-a3eb4f154e71
date added to LUP
2019-07-08 09:14:17
date last changed
2019-07-30 05:06:14
@article{3ff277a5-2dc1-48ef-8033-a3eb4f154e71,
  abstract     = {<p>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 &lt; 0.001) and higher level expression of CD40L in T cell (P &lt; 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 &lt; 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 &lt; 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.</p>},
  articleno    = {e12776},
  author       = {Sarmiento, Luis and Svensson, Johan and Barchetta, Ilaria and Giwercman, Aleksander and Cilio, Corrado M.},
  issn         = {0300-9475},
  keyword      = {autoimmunity,blood,human,T cells},
  language     = {eng},
  publisher    = {Wiley-Blackwell},
  series       = {Scandinavian Journal of Immunology},
  title        = {Copy number of the X-linked genes TLR7 and CD40L influences innate and adaptive immune responses},
  url          = {http://dx.doi.org/10.1111/sji.12776},
  year         = {2019},
}