The X-files of inflammation: Cellular mosaicism of X-linked polymorphic genes and the female advantage in the host response to injury and infection

Research output: Contribution to journalReview articlepeer-review

68 Scopus citations

Abstract

Females as compared with males display better general health status, longevity, and improved clinical course after injury and infection. It is generally believed that the female advantage is associated with the effects of sex hormones. This review argues that the sex benefit of females during the host response is associated with polymorphism of X-linked genes and cellular mosaicism for X-linked parental alleles. Cells from females carry both parental X chromosomes (maternal, Xm; or paternal, Xp), whereas males carry only one (Xm). Because of dosage compensation and random X inactivation, half of the cells from females express either Xm or Xp. Therefore, females are cellular mosaics for their X-linked polymorphic genes. This cellular mosaicism in females represents a more adaptive and balanced cellular machinery that is advantageous during the innate immune response. Several genes encoding key metabolic and regulatory proteins reside on the X chromosome, including members of the apoptotic cascade, hormone homeostasis, glucose metabolic enzymes, superoxide-producing machinery, and the toll-like receptor/nuclear factor κB/c-Jun N-terminal kinase signaling pathway. Polymorphic forms of these X-linked proteins are likely to manifest in phenotypic differences in the mosaic cell populations in females and may contribute to sex-related differences in the host response to injury and infection. The unique inheritance pattern of X-linked polymorphisms and their potential confounding effects in clinical trials are also discussed; furthermore, we present potential biomarkers for studying mosaic cell populations of innate immunity.

Original languageEnglish (US)
Pages (from-to)597-604
Number of pages8
JournalShock
Volume27
Issue number6
DOIs
StatePublished - Jun 2007

All Science Journal Classification (ASJC) codes

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

Keywords

  • Bruton kinase
  • G6PD
  • IRAK
  • Infection
  • Mosaicism
  • NEMO
  • NF-κB
  • SNP
  • Sepsis
  • Sex
  • X chromosome

Fingerprint

Dive into the research topics of 'The X-files of inflammation: Cellular mosaicism of X-linked polymorphic genes and the female advantage in the host response to injury and infection'. Together they form a unique fingerprint.

Cite this