Passagem-Santos, D.; Bonnet, M.; Sobral, D.; Trancoso, I.; Silva, J.G.; Barreto, V.M.; Athanasiadis, A.; Demengeot, J.; Pereira-Leal, J.B.
The RAG recombinase is a domesticated transposable element co-opted in jawed vertebrates to drive the process of the so-called V(D)J recombination, which is the hallmark of the adaptive immune system to produce antigen receptors. RAG targets, namely, the Recombination Signal Sequences (RSS), are rather long and degenerated sequences, which highlights the ability of the recombinase to interact with a wide range of target sequences, including outside of antigen receptor loci. The recognition of such cryptic targets by the recombinase threatens genome integrity by promoting aberrant DNA recombination, as observed in lymphoid malignancies. Genomes evolution resulting from RAG acquisition is an...
Breser, Maria L.; Lino, Andreia C.; Motrich, Ruben D.; Godoy, Gloria J.; Demengeot, Jocelyne; Rivero, Virginia E.
Susceptibility to autoimmune diseases results from the encounter of a complex and long evolved genetic context with a no less complex and changing environment. Major actors in maintaining health are regulatory T cells (Treg) that primarily dampen a large subset of autoreactive lymphocytes escaping thymic negative selection. Here, we directly asked whether Treg participate in defining susceptibility and resistance to Experimental Autoimmune Prostatitis (EAP). We analyzed three common laboratory strains of mice presenting with different susceptibility to autoimmune prostatitis upon immunization with prostate proteins. The NOD, the C57BL/6 and the BALB/c mice that can be classified along a disease score...
Costa, Nuno; Pires, Ana E; Gabriel, Ana M; Goulart, Luiz F; Pereira, Clara; Leal, Barbara; Queiros, Ana C; Chaara, Wahiba; Moraes-Fontes, Maria F; Vasconcelos, Carlos; Ferreira, Carlos; Martins, Jorge; Bastos, Marina; Santos, Maria J; Pereira, Maria A; Martins, Berta; Lima, Margarida; João, Cristina; Six, Adrien; Demengeot, Jocelyne; Fesel, Constantin
Fesel, Constantin; Barreto, Marta; Ferreira, Ricardo C.; Costa, Nuno; Venda, Lara L.; Pereira, Clara; Carvalho, Claudia; Morães-Fontes, Maria Francisca; Ferreira, Carlos M.; Vasconcelos, Carlos; Viana, João F.; Santos, Eugenia; Martins, Berta; Demengeot, Jocelyne; Vicente, Astrid M.
In human systemic lupus erythematosus (SLE), diverse autoantibodies accumulate over years before disease manifestation. Unaffected relatives of SLE patients frequently share a sustained production of autoantibodies with indiscriminable specificity, usually without ever acquiring the disease. We studied relations of IgG autoantibody profiles and peripheral blood activated regulatory T-cells (aTregs), represented by CD4(+)CD25(bright) T-cells that were regularly 70-90% Foxp3(+). We found consistent positive correlations of broad-range as well as specific SLE-associated IgG with aTreg frequencies within unaffected relatives, but not patients or unrelated controls. Our interpretation: unaffected relatives with shared genetic factors compensated pathogenic effects by aTregs engaged in parallel with...
Faustino, Lucas; Mucida, Daniel; Keller, Alexandre Castro; Demengeot, Jocelyne; Bortoluci, Karina; Sardinha, Luiz Roberto; Carla Takenaka, Maisa; Basso, Alexandre Salgado; Faria, Ana Maria Caetano; Russo, Momtchilo
Foxp3(+)CD25(+)CD4(+) regulatory T cells are vital for peripheral tolerance and control of tissue inflammation. In this study, we characterized the phenotype and monitored the migration and activity of regulatory T cells present in the airways of allergic or tolerant mice after allergen challenge. To induce lung allergic inflammation, mice were sensitized twice with ovalbumin/aluminum hydroxide gel and challenged twice with intranasal ovalbumin. Tolerance was induced by oral administration of ovalbumin for 5 consecutive days prior to OVA sensitization and challenge. We detected regulatory T cells (Foxp3(+)CD25(+)CD4(+) T cells) in the airways of allergic and tolerant mice; however, the number of...
Caramalho, I.; Lopes-Carvalho, T.; Ostler, D.; Zelenay, S.; Haury, M; Demengeot, J
Regulatory CD4 T cells (Treg) control inflammatory reactions to commensal bacteria and opportunist pathogens. Activation of Treg functions during these processes might be mediated by host-derived proinflammatory molecules or directly by bacterial products. We tested the hypothesis that engagement of germline-encoded receptors expressed by Treg participate in the triggering of their function. We report that the subset of CD4 cells known to exert regulatory functions in vivo (CD45RB(low) CD25(+)) selectively express Toll-like receptors (TLR)-4, -5, -7, and -8. Exposure of CD4(+) CD25(+) cells to the TLR-4 ligand lipopolysaccharide (LPS) induces up-regulation of several activation markers and enhances their survival/proliferation. This...
Barreto, M.; Ferreira, RC.; Lourenço, L.; Moraes-Fontes, MF.; Santos, E.; Alves, M.; Carvalho, C.; Martins, B.; Andreia, R.; Viana, JF.; Vasconcelos, C.; Mota-Vieira, L.; Ferreira, C.; Demengeot, J.; Vicente, AM.
Background: CD4(+)CD25(+) regulatory T cells play an essential role in maintaining immune homeostasis and preventing autoimmunity. Therefore, defects in Treg development, maintenance or function have been associated with several human autoimmune diseases including Systemic Lupus Erythematosus (SLE), a systemic autoimmune disease characterized by loss of tolerance to nuclear components and significantly more frequent in females.
Carvalho, Thiago L.; Mota-Santos, Tomaz; Cumano, Ana; Demengeot, Jocelyne; Paulo, Vieira
Interleukin 7 is a crucial factor for the development of murine T and B lymphocytes. We now
report that, in the absence of interleukin 7, B lymphocyte production takes place exclusively
during fetal and perinatal life, ceasing after 7 wk of age. In peripheral organs, however, the pool
of B lymphocytes is stable throughout adult life and consists only of cells that belong to the B1
and marginal zone (MZ) compartments. This is accompanied by a 50-fold increase in the frequency
of immunoglobulin (Ig)M- and IgG-secreting cells, and the concentration of serum
immunoglobulins is increased three- to fivefold. Both the MZ phenotype and the increase in