- Dr. Maria-Cristina Cuturi, Principal Investigator
- Dr. Josien Régis, Co-Applicant
- Dr. Chiffoleau Elise, Research Associate
- Dr. Heslan Jean-Marie, Research Associate
- Mr. Condamine Thomas, Master Student
- INSERM, Nantes, France
- Characterization of Tolerance-Related and Induced Transcript, a New Member of the CD20 family
The Gene Search system tool was used to identify new molecules in a model of allograft tolerance and develop new means of promoting long-term acceptance of allografts and improve the outcome of organ transplantation. We cloned the cDNA for a rat gene specifically expressed in graft-infiltrating cells in tolerated allografts. We named it TORID, for tolerance-related and induced transcript. Analysis of the predicted amino acid sequence of TORID and its human counterpart LR8, showed despite a distinct chromosomal location, a yet undescribed homology with the four-transmembrane CD20/FcεRIβ family proteins.
TORID mRNA is found in a number of rat tissues and lymphoid organs especially. Among the different subpopulations of freshly isolated leukocytes, macrophages and dendritic cells (DCs), a strong expression of TORID was found. TORID protein localizes to the nuclear envelope, which suggests an intracellular function. Interestingly, expression of TORID is dramatically decreased following macrophage or DC maturation/activation, and over-expression of TORID in DCs through viral transduction induces the development of immature cells refractory to further stimulation. Moreover, infection of allografts with an adenovirus encoding TORID significantly prolongs allograft survival. This suggests that TORID may be involved in functions of immature myeloid cells, and processes of induction or maintenance of allograft tolerance.
This project addresses the expression and functional role of TORID in immune responses particularly in transplantation using different approaches of over-expression and inhibition of gene expression. Characterization of TORID may lead to the development of a new means of promoting long-term acceptance of allografts.