Linkage analysis of the genetic determinants of T-cell IL-4 secretion, and identification of Flj20274 as a putative candidate gene

P Choi, D Xanthaki, SJ Rose, M Haywood, H Reiser, Bernard J Morley

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The activation-induced differentiation of naive CD4+ T cells generates functionally divergent type 1 helper T cells (Th1) or type 2 helper T cells (Th2) effector cell populations, characterized by secretion of Interferon (IFN)-gamma or Interleukin (IL)-4, respectively. Inappropriate generation of Th subsets may contribute to immune dysfunction. The decision to generate Th1/Th2 lineages is critically regulated by cytokines, such that IL-12 induces Th1 differentiation, while IL-4 induces Th2 differentiation. Genetic factors influence the pathway of Th differentiation, as displayed by the preferential generation of divergent Th populations by different inbred strains of mice. We employ two complementary genetic techniques to identify genes that regulate the default IL-4 secretion profiles of T cells from BALB/c and B6 mice. We performed a genome-wide linkage analysis of the progeny of a backcross between BALB/c and B6 mice to identify three loci, T-cell secretion of interleukin-4 (Tsi)1-3, on chromosomes 7, 19 and 15, respectively, which regulate in vitro T-cell IL-4 production. We have also employed mRNA representational difference analysis to isolate a gene, Flj20274, which is differentially expressed in T cells that secrete high levels of IL-4. Significantly, Flj20274 was mapped to the point of peak linkage within Tsi1 and is a strong candidate for Tsi1.
Original languageEnglish
Pages (from-to)290-297
Number of pages8
JournalGenes and Immunity
Volume6
DOIs
Publication statusPublished - Jun 2005

Fingerprint

Genetic Linkage
Interleukin-4
T-Lymphocytes
Genes
Th2 Cells
Chromosomes, Human, Pair 19
Genetic Techniques
Chromosomes, Human, Pair 15
Th1 Cells
Inbred Strains Mice
Chromosomes, Human, Pair 7
Interleukin-12
Interleukin-1
Population
Interferon-gamma
Genome
Cytokines
Messenger RNA

Keywords

  • cytokines
  • cellular differentiation
  • Th1/Th2 cells

Cite this

Linkage analysis of the genetic determinants of T-cell IL-4 secretion, and identification of Flj20274 as a putative candidate gene. / Choi, P; Xanthaki, D; Rose, SJ; Haywood, M; Reiser, H; Morley, Bernard J.

In: Genes and Immunity, Vol. 6, 06.2005, p. 290-297.

Research output: Contribution to journalArticle

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