LIMLE, a new molecule over-expressed following activation, is involved in the stimulatory properties of dendritic cells.
Dendritic cells are sentinels of the immune system distributed throughout the body, that following danger signals will migrate to secondary lymphoid organs to induce effector T cell responses. We have identified, in a rodent model of graft rejection, a new molecule expressed by dendritic cells that we have named LIMLE (RGD1310371). To characterize this new molecule, we analyzed its regulation of expression and its function. We observed that LIMLE mRNAs were rapidly and strongly up regulated in dendritic cells following inflammatory stimulation. We demonstrated that LIMLE inhibition does not alter dendritic cell maturation or cytokine production following Toll-like-receptor stimulation. However, it reduces their ability to stimulate effector T cells in a mixed leukocyte reaction or T cell receptor transgenic system. Interestingly, we observed that LIMLE protein localized with actin at some areas under the plasma membrane. Moreover, LIMLE is highly expressed in testis, trachea, lung and ciliated cells and it has been shown that cilia formation bears similarities to formation of the immunological synapse which is required for the T cell activation by dendritic cells. Taken together, these data suggest a role for LIMLE in specialized structures of the cytoskeleton that are important for dynamic cellular events such as immune synapse formation. In the future, LIMLE may represent a new target to reduce the capacity of dendritic cells to stimulate T cells and to regulate an immune response.
INSERM, U1064, Nantes, France; CHU Nantes, Institut de Transplantation et de Recherche en Transplantation, ITUN, Nantes, France; Université de Nantes, Faculté de Médecine, Nantes, France.
Laëtitia
L
Le Texier
INSERM, U1064, Nantes, France; CHU Nantes, Institut de Transplantation et de Recherche en Transplantation, ITUN, Nantes, France; Université de Nantes, Faculté de Médecine, Nantes, France.
Justine
J
Durand
INSERM, U1064, Nantes, France; CHU Nantes, Institut de Transplantation et de Recherche en Transplantation, ITUN, Nantes, France; Université de Nantes, Faculté de Médecine, Nantes, France.
Amélie
A
Lavault
Plateforme MicroPICell, SFR santé, Nantes, France.
Philippe
P
Hulin
Plateforme GenOuest, IRISA-INRIA, Campus de Beaulieu, Rennes, France.
Olivier
O
Collin
Plateforme GenOuest, IRISA-INRIA, Campus de Beaulieu, Rennes, France.
Yvan
Y
Le Bras
INSERM, U1064, Nantes, France; CHU Nantes, Institut de Transplantation et de Recherche en Transplantation, ITUN, Nantes, France; Université de Nantes, Faculté de Médecine, Nantes, France.
Maria-Cristina
MC
Cuturi
INSERM, U1064, Nantes, France; CHU Nantes, Institut de Transplantation et de Recherche en Transplantation, ITUN, Nantes, France; Université de Nantes, Faculté de Médecine, Nantes, France.
Elise
E
Chiffoleau
D000199:Actins / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D019295:Computational Biology; D016207:Cytokines / Q000276:immunology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D054992:Immunological Synapses / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009841:Oligonucleotides / Q000235:genetics; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051193:Toll-Like Receptors / Q000276:immunology
D000199:Actins; D016207:Cytokines; D003598:Cytoskeletal Proteins; C000594110:LIMLE protein, rat; D009841:Oligonucleotides; D051193:Toll-Like Receptors