Faculty Collaboration Database

A locus on mouse chromosome 13 inversely regulates CD1d expression and the development of invariant natural killer T-cells. Genes Immun 2015;16(3):221-30

Date

02/06/2015

Pubmed ID

25654212

Pubmed Central ID

PMC4409484

DOI

10.1038/gene.2014.81

Scopus ID

2-s2.0-84928582595 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

Invariant natural killer T (iNKT)-cell development is controlled by many polymorphic genes present in commonly used mouse inbred strains. Development of type 1 diabetes (T1D) in NOD mice partly results from their production of fewer iNKT-cells compared with non-autoimmune-prone control strains, including ICR. We previously identified several iNKT-cell quantitative trait genetic loci co-localized with known mouse and human T1D regions in a (NOD × ICR)F2 cross. To further dissect the mechanisms underlying the impaired iNKT-cell compartment in NOD mice, we carried out a series of bone marrow transplantation as well as additional genetic mapping studies. We found that impaired iNKT-cell development in NOD mice was mainly due to the inability of their double-positive (DP) thymocytes to efficiently select this T-cell population. Interestingly, we observed higher levels of CD1d expression by NOD than by ICR DP thymocytes. The genetic control of the inverse relationship between the CD1d expression level on DP thymocytes and the frequency of thymic iNKT-cells was further mapped to a region on chromosome 13 between 60.12 and 70.59 Mb. The NOD allele was found to promote CD1d expression and suppress iNKT-cell development. Our results indicate that genetically controlled physiological variation of CD1d expression levels modulates iNKT-cell development.

Author List

Tsaih SW, Presa M, Khaja S, Ciecko AE, Serreze DV, Chen YG

Authors

Yi-Guang Chen PhD Professor in the Pediatrics department at Medical College of Wisconsin
Shirng-Wern Tsaih Research Scientist II in the Obstetrics and Gynecology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Antigens, CD
Antigens, CD1d
Cell Differentiation
Chromosome Mapping
Chromosomes, Mammalian
Gene Expression Regulation
Lymphocyte Count
Mice
Mice, Inbred ICR
Mice, Inbred NOD
Models, Animal
Natural Killer T-Cells
Phenotype
Quantitative Trait Loci
Receptors, Antigen, T-Cell
Receptors, Cell Surface
Signaling Lymphocytic Activation Molecule Family Member 1
Thymocytes