Journal
CELLS
Volume 10, Issue 6, Pages -Publisher
MDPI
DOI: 10.3390/cells10061367
Keywords
TCL1A; kidney transplantation; tolerance; Breg; Akt; IL-10
Categories
Funding
- EU-TRAIN project from the European Union's Horizon 2020 Research and Innovation Programme [754995]
- LabEx IGO project - ''Investissements d'Avenir'' French Government program [ANR-11-LABX-0016-01]
- Marie Sklodowska-Curie fellowship (IF-EF) from the European Union's Horizon 2020 Research and Innovation Programme [706296]
- IHU-Cesti project [ANR-10-IBHU-005]
- ANR [ANR-18-CE170019]
- ANR project BIKET [ANR-17-CE17-0008]
- ANR project KTD-innov [ANR-17-RHUS-0010]
- Nantes Metropole
- Institut de Recherche en Sante Respiratoire des Pays de la Loire (IRSR-PL)
- Fonds de Recherche en Sante Respiratoire under the patronage of the Fondation du Souffle (Paris) under the patronage of the Fondation du Souffle
- Region Pays de la Loire
- Marie Curie Actions (MSCA) [706296] Funding Source: Marie Curie Actions (MSCA)
- Agence Nationale de la Recherche (ANR) [ANR-17-RHUS-0010] Funding Source: Agence Nationale de la Recherche (ANR)
- H2020 Societal Challenges Programme [754995] Funding Source: H2020 Societal Challenges Programme
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Despite the progress in kidney transplantation, the issue of life-long immunosuppressive therapies remains a concern. Operational tolerance, which refers to allograft acceptance without immunosuppression, has been the focus of research to better understand post-transplantation mechanisms. TCL1A, a potential biomarker for operational tolerance, has been found to be overexpressed in the peripheral blood of tolerant patients and may play a role in the establishment and maintenance of renal allograft tolerance.
Despite much progress in the management of kidney transplantation, the need for life-long immunosuppressive therapies remains a major issue representing many risks for patients. Operational tolerance, defined as allograft acceptance without immunosuppression, has logically been subject to many investigations with the aim of a better understanding of post-transplantation mechanisms and potentially how it would be induced in patients. Among proposed biomarkers, T-cell Leukemia/Lymphoma protein 1A (TCL1A) has been observed as overexpressed in the peripheral blood of operational tolerant patients in several studies. TCL1A expression is restricted to early B cells, also increased in the blood of tolerant patients, and showing regulatory properties, notably through IL-10 secretion for some subsets. TCL1A has first been identified as an oncogene, overexpression of which is associated to the development of T and B cell cancer. TCL1A acts as a coactivator of the serine threonine kinase Akt and through other interactions favoring cell survival, growth, and proliferation. It has also been identified as interacting with others major actors involved in B cells differentiation and regulation, including IL-10 production. Herein, we reviewed known interactions and functions of TCL1A in B cells which could involve its potential role in the set up and maintenance of renal allograft tolerance.
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