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


Reference:

Choi, P., Xanthaki, D., Rose, S., Haywood, M., Reiser, H. and Morley, B. J., 2005. Linkage analysis of the genetic determinants of T-cell IL-4 secretion, and identification of Flj20274 as a putative candidate gene. Genes and Immunity, 6, pp. 290-297.

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Official URL:

http://dx.doi.org/10.1038/sj.gene.6364192

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.

Details

Item Type Articles
CreatorsChoi, P., Xanthaki, D., Rose, S., Haywood, M., Reiser, H. and Morley, B. J.
DOI10.1038/sj.gene.6364192
Uncontrolled Keywordscytokines, cellular differentiation, th2 cells
DepartmentsUniversity Administration & Central Services > Vice-Chancellor's Office
RefereedYes
StatusPublished
ID Code19271

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