Biology subjects

Cheynier, R.

Publications and source records attributed to Cheynier, R..

3 recordsLinked to original sources

bioRxiv2022

Low memory T cells blood counts and high naive regulatory T cells percentage at relapsing remitting multiple sclerosis diagnosis

ObjectiveTo assess the peripheral immune system of newly diagnosed relapsing remitting multiple sclerosis (RRMS) patients and compare it to healthy controls (HC). MethodsCross-sectional study with 30 treatment-naive newly diagnosed RRMS patients, and 33 sex and age-matched HC. Their peripheral blood mononuclear cells were analysed regarding: i) thymic function surrogates [T cell receptor excision circles (TRECs) and recent thymic emigrants (RTEs)]; ii) naive and memory CD4+ and CD8+ T cells subsets; iii) T helper (Th) phenotype and chemokine receptors expression on T cells subsets; iv) regulatory T cell (Tregs) phenotype; and vi) expression of activating/inhibitory receptors by natural killer (NK) and NKT cells. Analyses were controlled for age, sex, and human cytomegalovirus (HCMV) IgG seroprevalence. ResultsNewly diagnosed RRMS patients and HC have equivalent thymic function as determined by similar numbers of RTEs, and levels of sjTRECs, DJ{beta}TRECs and sj/DJ{beta}TREC ratio. In the CD8+ T cells compartment RRMS patients have a higher naive/memory ratio and lower memory cell counts in blood, specifically of effector memory and TemRA CD8+ T cells. Among CD4+ T cells lower blood counts of effector memory cells are found in patients upon controlling for sex, age and HCMV IgG seroprevalence. RRMS patients have higher percentage of naive Tregs comparing to HC. Percentages of immature CD56bright NK cells expressing the inhibitory receptor KLRG1, and of mature CD56dimCD57+ NK cells expressing NKp30 are higher in patients. No major alterations are observed on NKT cells. MS severity and time from relapse correlate with immune cells alterations. ConclusionCharacterization of the peripheral immune system of treatment-naive newly diagnosed RRMS patients unveiled immune features present at clinical onset including lower memory T cells blood counts, particularly among CD8+ T cells, higher percentage of naive Tregs and altered percentages of NK cells subsets expressing inhibitory or activating receptors. These findings might set the basis to better understand disease pathogenesis.

immunology↗

bioRxiv2020

IL-7-adjuvanted vaginal vaccine elicits strong mucosal immune responses in non-human primates

Mucosal immune responses are crucial in protecting against pathogens entering through mucosal surfaces. However, due to difficulties in disrupting the tolerogenic environment associated with mucosa, mucosal immunity remains difficult to stimulate through vaccines and requires appropriate adjuvants. We previously demonstrated that either administered systemically to healthy macaques or locally expressed in the intestinal mucosa of acutely SIV-infected macaques, interleukin-7 (IL-7) triggers chemokine expression and immune cell homing into mucosae, suggesting its important role in the development of mucosal immune responses. We therefore examined whether local delivery of recombinant glycosylated simian IL-7 (rs-IL-7gly) to the vaginal mucosa of rhesus macaques could prepare the lower female genital tract (FGT) for subsequent immunization and act as an efficient mucosal adjuvant. First, we showed that local administration of rs-IL-7gly triggers vaginal overexpression of chemokines and infiltration of mDCs, macrophages, NKs, B- and T-cells in the chorion while MamuLa-DR+ APCs accumulated in the epithelium. Subsequent mucosal anti-DT immunization in macaques resulted in a faster, stronger, and more persistent mucosal antibody response compared to DT-immunization alone. Indeed, we detected robust productions of DT-specific IgAs and IgGs in their vaginal secretions and identified cells secreting DT-specific IgAs in their vaginal mucosa and IgGs in draining lymph nodes. Finally, the expression of chemokines involved in the organization of tertiary lymphoid structures (TLS) was only increased in the vaginal mucosa of IL-7-adjuvanted immunized macaques. Interestingly, TLSs developed around PNAd+ high endothelial venules in their lower FGT sampled 2 weeks after the last immunization. Non-traumatic vaginal administration of rs-IL-7gly prepares the mucosa to respond to subsequent local immunization and allows the development of a strong mucosal immune response in macaques, through the chemokine-dependent recruitment of immune cells, the activation of mDCs and the formation of TLSs. The localization of DT-specific IgA plasma cells in the mucosa argues for their contribution to the production of specific immunoglobulins in the vaginal secretions. Our results highlight the potential of IL-7 as a potent mucosal adjuvant to stimulate the FGT immune system and elicit vaginal antibody responses to local immunization, which is the most promising way to confer protection against many sexually transmitted diseases.

immunology↗

bioRxiv2017

Stage-specific ISG expression reveals functional convergence of type I and II IFNs in SIV infection

AbstractInterferons play a major role in controlling viral infections including HIV/SIV infections. Persistent up-regulation of interferon-stimulated-genes (ISGs) is associated with chronic immune activation and progression in SIV/HIV infections, but the respective contribution of different IFNs is unclear. We analyzed the expression of annotated IFN-induced genes in SIV-infected macaques to decrypt the respective roles of type-I (,{beta}) and type-II ({gamma}) IFNs. Both IFN types were induced in lymph nodes during early stage of primary infection. Induction of type-II IFN persisted during the chronic phase, in contrast to undetectable induction of type-I IFN. Interferome-based analysis of ISGs revealed that at both acute and chronic infection phases most differentially expressed ISGs were inducible by both type-I and type-II IFNs and displayed the highest increases, indicating strong convergence and synergy between type-I and type-II IFNs. The analysis of functional signatures of ISG expression revealed temporal changes in IFN expression patterns identifying phase-specific ISGs. These results suggest that IFN-{gamma} strongly contribute to shape ISG upregulation in addition to type-I IFN and may contribute to progression.

immunology↗