Identification of a new member of the CD20/FcepsilonRIbeta family overexpressed in tolerated allografts.
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 tolerance-related 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/FcepsilonRIbeta 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 marrow-derived 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.
Louvet
Cédric
C
Institut National de la Santé et de la Recherche Médicale (INSERM), Unit 643 and Institut de Transplantation et de Recherche en Transplantation (ITERT), Nantes, France.
Chiffoleau
Elise
E
Heslan
Michèle
M
Tesson
Laurent
L
Heslan
Jean-Marie
JM
Brion
Régis
R
Bériou
Gaëlle
G
Guillonneau
Carole
C
Khalife
Jamal
J
Anegon
Ignacio
I
Cuturi
Maria-Cristina
MC
D000256:Adenoviridae / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D018951:Antigens, CD20 / Q000737:chemistry / Q000378:metabolism*; D001803:Blood Transfusion; D001854:Bone Marrow Cells / Q000166:cytology; D019070:Cell Lineage; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology; D015536:Down-Regulation; D018014:Gene Transfer Techniques; D006084:Graft Rejection; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D018664:Interleukin-12 / Q000378:metabolism; D053762:Interleukin-12 Subunit p40; D008213:Lymphocyte Activation; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology; D005810:Multigene Family; D009693:Nucleic Acid Hybridization; D009841:Oligonucleotides / Q000737:chemistry; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D021122:Protein Subunits / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D017455:Receptors, IgE / Q000737:chemistry / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013154:Spleen / Q000378:metabolism; D013997:Time Factors; D023001:Transplantation Tolerance; D014184:Transplantation, Homologous / Q000379:methods*
D018951:Antigens, CD20; D018076:DNA, Complementary; D053762:Interleukin-12 Subunit p40; D009841:Oligonucleotides; D021122:Protein Subunits; D012333:RNA, Messenger; D017455:Receptors, IgE; C507364:Tmem176b protein, rat; D049452:Green Fluorescent Proteins; D018664:Interleukin-12