A novel CD93 polymorphism in non-obese diabetic NOD and NZB-W F1 mice is linked to a CD4 iNKT cell deficient stateReportar como inadecuado




A novel CD93 polymorphism in non-obese diabetic NOD and NZB-W F1 mice is linked to a CD4 iNKT cell deficient state - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Immunogenetics

, Volume 62, Issue 6, pp 397–407

First Online: 13 April 2010Received: 09 November 2009Accepted: 16 March 2010

Abstract

In the present study, we characterize a polymorphism in the CD93 molecule, originally identified as the receptor for the C1q complement component i.e., C1qRp, or AA4.1 in non-obese diabetic NOD mice. This allele carries a coding polymorphism in the first epidermal growth factor-like domain of CD93, which results in an amino acid substitution from Asn→His at position 264. This polymorphism does not appear to influence protein translation or ecto-domain cleavage, as CD93 is detectable in bone-marrow-derived macrophage and B-cell precursor lysates and in soluble form in the serum. The NOD CD93 isoform causes a phenotypic aberrancy in the early B-cell developmental stages i.e., pro-, pre-, immature, and transitional, likely related to a conformational variation. Interestingly, the NZB-W F1 strain, which serves as a murine model of Lupus, also expresses an identical CD93 sequence polymorphism. Cd93 is located within the NOD Idd13 locus and is also tightly linked to the NZB-W F1 Wbw1 and Nkt2 disease susceptibility loci, which are thought to regulate natural killer T NKT cell homeostasis. Consistent with this genetic linkage, we found B6 CD93 and B6.NOD mice to be susceptible to a profound CD4 NKT cell deficient state. These data suggest that Cd93 may be an autoimmune susceptibility gene residing within the Idd13 locus, which plays a role in regulating absolute numbers of CD4 NKT cells.

KeywordsNOD mice Idd13 NZB-W F1 mice Nkt2 CD93 iNKT cells AbbreviationsBMBone marrow

TRTransitional

MZMarginal zone

iNKT cellInvariant natural killer T cell

NODNon-obese diabetic

DNDouble negative

CD4SPCD4 single positive

IddInsulin-dependent diabetes

alpha-GalCerAlpha-galactosyl ceramide

LLPCLong-lived plasma cell

Ghazal Zekavat and Raha Mozaffari contributed equally to this study.

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Autor: Ghazal Zekavat - Raha Mozaffari - Vanessa J. Arias - Susan Y. Rostami - Armen Badkerhanian - Andrea J. Tenner - Kim E. 

Fuente: https://link.springer.com/







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