Identification of a New Member of the CD20/FcεRIβ Family Overexpressed in Tolerated Allografts

Abstract

We identified a novel rat gene specifically overexpressed in tolerated heart allografts in a model of tolerance induced by donor-specific blood transfusion (DST). We named this gene TORID, for tolerancerelated and induced transcript. We show that TORID expression can be attributed to non-T cells infiltrating tolerated grafts. Interestingly, TORID overexpression was also observed in long-term grafts from a different model of tolerance in which chronic rejection does not occur. Comparison of the predicted amino acid sequence of TORID and of its human counterpart LR8 showed an homology with the four-transmembrane CD20/FceRIb family proteins. We investigated TORID expression in naive rat immune cells and lymphoid tissues. TORID was found to be preferentially expressed in cells of the myeloid lineage such as macrophages and dendritic cells (DCs). Its expression dramatically decreased following activation/maturation. Similar results were obtained in human monocyte-derived DCs. Interestingly, TORID overexpression in bone marrowderived DCs alters expression of MHC II and CD86 and production of IL12p40 following activation. These results suggest that TORID may be involved in the control of DC maturation and may, therefore, play a role in the induction or maintenance of allograft tolerance.

B-Cell-Related Biomarkers of Tolerance are Up-Regulated in Rejection-Free Kidney Transplant Recipients

“…Because this molecule was preferentially expressed on resting macrophages and dendritic cells, we can only speculate as to its role in active tolerogenic pathways (23). Our observation demonstrating increased expression of this gene in blood of patients with acute rejection suggested that it was associated with alloantigen presentation and inflammation, suggesting that the tolerogenic potential of this molecule remains to be defined.…”

“…One of the genes analyzed, TMEM176B, originally described as TORID, was described as overexpressed in tolerated heart allografts in a model of tolerance induced by donorspecific blood transfusion with long-term survival without signs of chronic rejection (23). Because this molecule was preferentially expressed on resting macrophages and dendritic cells, we can only speculate as to its role in active tolerogenic pathways (23).…”

Abnormal accumulation of human transmembrane (TMEM)-176A and 176B proteins is associated with cancer pathology

“…Similar to TMEM176A, the level of human TMEM176B transcripts has been shown to be markedly elevated in transplanted livers that showed recurrence of HCV infection (Gehrau et al, 2011). On the other hand, the mRNA expression of rat Tmem176B (also known as rat TORID, or mouse Clast1/LR8) is highly correlated with tolerated allografts (transplanted tissue taken from a different individual of the same species) (Louvet et al, 2005; Condamine et al, 2010). This finding suggests that Tmem176B may be involved in the regulation of immune cell activation and tolerance (Louvet et al, 2005; Condamine et al, 2010).…”

“…On the other hand, the mRNA expression of rat Tmem176B (also known as rat TORID, or mouse Clast1/LR8) is highly correlated with tolerated allografts (transplanted tissue taken from a different individual of the same species) (Louvet et al, 2005; Condamine et al, 2010). This finding suggests that Tmem176B may be involved in the regulation of immune cell activation and tolerance (Louvet et al, 2005; Condamine et al, 2010). Indeed, the tissue mRNA expression profiles of rat and mouse Tmem176A or Tmem176B point to an important role in immune function.…”

“…Indeed, the tissue mRNA expression profiles of rat and mouse Tmem176A or Tmem176B point to an important role in immune function. For example, both rodent Tmem176A and Tmem176B transcripts are detected preferentially in lymphoid tissues (lymph nodes, thymus, spleen, and bone marrow), lung, kidney, as well as certain types of myeloid and lymphoid cells (Louvet et al, 2005; Condamine et al, 2010; Ghosh et al, 2010). Inflammatory stimulation using lipopolysaccharide (LPS) or poly-I:C exposure of mouse bone marrow-derived dendritic cells (BMDCs) results in down-regulation of Tmem176A and 176B transcript levels (Condamine et al, 2010).…”