Publications
2018
Sawaf Matthieu, Fauny Jean-Daniel, Felten Renaud, Sagez Flora, Gottenberg Jacques-Eric, Dumortier Hélène, Monneaux Fanny
Defective BTLA functionality is rescued by restoring lipid metabolism in lupus CD4+ Ŧ cells Journal Article
In: JCI insight, vol. 3, no. 13, 2018, ISSN: 2379-3708.
Abstract | Links | BibTeX | Tags: 80 and over, Adolescent, Adult, Aged, Autoimmune Diseases, Autoimmunity, CD4-Positive T-Lymphocytes, Cell Proliferation, CTLA-4 Antigen, Dumortier, Female, France, Humans, I2CT, Imagerie, Immunologic, Immunology, Lipid Metabolism, lupus, Lupus Erythematosus, Lymphocyte Activation, Male, Middle Aged, Monneaux, Programmed Cell Death 1 Receptor, Receptors, Signal Transduction, Systemic, Team-Dumortier, Young Adult
@article{sawaf_defective_2018,
title = {Defective BTLA functionality is rescued by restoring lipid metabolism in lupus CD4+ Ŧ cells},
author = {Matthieu Sawaf and Jean-Daniel Fauny and Renaud Felten and Flora Sagez and Jacques-Eric Gottenberg and Hélène Dumortier and Fanny Monneaux},
doi = {10.1172/jci.insight.99711},
issn = {2379-3708},
year = {2018},
date = {2018-01-01},
journal = {JCI insight},
volume = {3},
number = {13},
abstract = {Coinhibitory receptors play an important role in the prevention of autoimmune diseases, such as systemic lupus erythematosus (SLE), by limiting T cell activation. B and T lymphocyte attenuator (BTLA) is an inhibitory receptor, similar to cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD1), that negatively regulates the immune response. The role of BTLA in the pathogenesis of autoimmune diseases in humans and, more specifically, in SLE is largely unknown. We investigated BTLA expression on various T cell subsets, and we did not observe significant variations of BTLA expression between lupus patients and healthy controls. However, the enhancement of BTLA expression after activation was significantly lower in SLE patients compared with that in healthy controls. Furthermore, we found an impaired capacity of BTLA to inhibit T cell activation in SLE due to a poor BTLA recruitment to the immunological synapse following T cell stimulation. Finally, we demonstrated that defective BTLA function can be corrected by restoring intracellular trafficking and by normalizing the lipid metabolism in lupus CD4+ T cells. Collectively, our results evidence that the BTLA signaling pathway is altered in SLE T cells and highlight the potential of targeting this pathway for the development of new therapeutic strategies in lupus.},
keywords = {80 and over, Adolescent, Adult, Aged, Autoimmune Diseases, Autoimmunity, CD4-Positive T-Lymphocytes, Cell Proliferation, CTLA-4 Antigen, Dumortier, Female, France, Humans, I2CT, Imagerie, Immunologic, Immunology, Lipid Metabolism, lupus, Lupus Erythematosus, Lymphocyte Activation, Male, Middle Aged, Monneaux, Programmed Cell Death 1 Receptor, Receptors, Signal Transduction, Systemic, Team-Dumortier, Young Adult},
pubstate = {published},
tppubtype = {article}
}
2008
Parietti Véronique, Monneaux Fanny, Décossas Marion, Muller Sylviane
Function of CD4+,CD25+ Treg cells in MRL/lpr mice is compromised by intrinsic defects in antigen-presenting cells and effector Ŧ cells Journal Article
In: Arthritis and Rheumatism, vol. 58, no. 6, pp. 1751–1761, 2008, ISSN: 0004-3591.
Abstract | Links | BibTeX | Tags: Animal, Animals, Antigen-Presenting Cells, Antigens, B7-1 Antigen, B7-2 Antigen, CD, Cell Communication, Cells, Coculture Techniques, CTLA-4 Antigen, Cultured, Disease Models, Female, I2CT, Interleukin-1, Interleukin-2 Receptor alpha Subunit, Lupus Erythematosus, Mice, Monneaux, Regulatory, Systemic, T-Lymphocyte Subsets, T-Lymphocytes, Team-Dumortier
@article{parietti_function_2008,
title = {Function of CD4+,CD25+ Treg cells in MRL/lpr mice is compromised by intrinsic defects in antigen-presenting cells and effector Ŧ cells},
author = {Véronique Parietti and Fanny Monneaux and Marion Décossas and Sylviane Muller},
doi = {10.1002/art.23464},
issn = {0004-3591},
year = {2008},
date = {2008-06-01},
journal = {Arthritis and Rheumatism},
volume = {58},
number = {6},
pages = {1751--1761},
abstract = {OBJECTIVE: Naturally occurring CD4+,CD25+ Treg cells are central in the maintenance of peripheral tolerance. Impaired activity and/or a lower frequency of these cells is involved in the emergence of autoimmunity. We undertook this study to analyze relative proportions and functional alterations of Treg cells in MRL/lpr mice.
METHODS: The frequency of CD4+,CD25+ T cells in the peripheral blood of healthy and autoimmune mice was compared by flow cytometry. The capacity of CD4+,CD25+ T cells to inhibit the proliferation and cytokine secretion of CD4+,CD25- T cells was assessed after polyclonal activation.
RESULTS: MRL/lpr mice exhibited a normal percentage of CD4+,CD25 high T cells, and forkhead box P3 messenger RNA and protein expression in Treg cells was not altered. However, MRL/lpr Treg cells displayed a reduced capacity to suppress proliferation and to inhibit interferon-gamma secretion by syngeneic effector CD4+,CD25- T cells, as compared with syngeneic cocultures of CBA/J T cells. Moreover, effector MRL/lpr CD4+,CD25- T cells were substantially less susceptible to suppression even when cultured with CBA/J or MRL/lpr Treg cells. Crossover experiments led us to conclude that in MRL/lpr mice, each partner engaged in T cell regulation displays altered functions. Molecules involved in suppressive mechanisms (CTLA-4 and CD80/CD86) are underexpressed, and antigen-presenting cells (APCs) produce raised levels of interleukin-6, which is known to abrogate suppression.
CONCLUSION: Our results suggest that although the frequency and phenotype of Treg cells in MRL/lpr mice are similar to those in normal mice, Treg cells in MRL/lpr mice are not properly stimulated by APCs and are unable to suppress proinflammatory cytokine secretion from effector T cells.},
keywords = {Animal, Animals, Antigen-Presenting Cells, Antigens, B7-1 Antigen, B7-2 Antigen, CD, Cell Communication, Cells, Coculture Techniques, CTLA-4 Antigen, Cultured, Disease Models, Female, I2CT, Interleukin-1, Interleukin-2 Receptor alpha Subunit, Lupus Erythematosus, Mice, Monneaux, Regulatory, Systemic, T-Lymphocyte Subsets, T-Lymphocytes, Team-Dumortier},
pubstate = {published},
tppubtype = {article}
}
METHODS: The frequency of CD4+,CD25+ T cells in the peripheral blood of healthy and autoimmune mice was compared by flow cytometry. The capacity of CD4+,CD25+ T cells to inhibit the proliferation and cytokine secretion of CD4+,CD25- T cells was assessed after polyclonal activation.
RESULTS: MRL/lpr mice exhibited a normal percentage of CD4+,CD25 high T cells, and forkhead box P3 messenger RNA and protein expression in Treg cells was not altered. However, MRL/lpr Treg cells displayed a reduced capacity to suppress proliferation and to inhibit interferon-gamma secretion by syngeneic effector CD4+,CD25- T cells, as compared with syngeneic cocultures of CBA/J T cells. Moreover, effector MRL/lpr CD4+,CD25- T cells were substantially less susceptible to suppression even when cultured with CBA/J or MRL/lpr Treg cells. Crossover experiments led us to conclude that in MRL/lpr mice, each partner engaged in T cell regulation displays altered functions. Molecules involved in suppressive mechanisms (CTLA-4 and CD80/CD86) are underexpressed, and antigen-presenting cells (APCs) produce raised levels of interleukin-6, which is known to abrogate suppression.
CONCLUSION: Our results suggest that although the frequency and phenotype of Treg cells in MRL/lpr mice are similar to those in normal mice, Treg cells in MRL/lpr mice are not properly stimulated by APCs and are unable to suppress proinflammatory cytokine secretion from effector T cells.