Lymphocytes T CD4+ régulateurs et polarisation immunitaire : étude appliquée à la dermatomyosite et au contexte des syndromes myélodysplasiques et la leucémie aiguë myéloïde en rechute après allogreffe

Regulatory CD4 + T cells (Treg) are essential for maintaining peripheral tolerance, preventing autoimmune diseases like dermatomyositis, and play a role in the anti-tumor response and prevention of graft versus host disease (graft versus host disease - GVHD) after allogeneic bone marrow transplantation. Using two markers associated with ATP metabolism, CD26 and CD39, and the CD45RA maturation marker, we separated the Treg into 5 distinct subpopulations, each representing a different stage of maturation. Micro-environmental factors dictate this maturation as well as the functions of these different sub-populations. Dermatomyositis is an autoimmune disease primarily affecting the skin and muscle. During this pathology, we observed a phenotypic modification of Treg with a decrease in CD25 expression and an accumulation of CD39+ populations. The study of immune polarization revealed the disappearance of circulating MAIT (mucosal-associated invariant T cells) cells, the existence of a similar lymphocyte profile between the classic form and the amyopathic form and a skin "type I interferon” polarization during anti-MDA5 associated with the presence of interferon kappa. Finally, we were interested in patients presenting with relapsing MDS or AML after allogeneic transplantation treated with azacytidine (AZA), a hypomethylating agent. We were able to show that the Treg phenotype was modified compared to ungrafted individuals, but that it did not differ between relapse and non-relapse. Treatment with AZA appears to have a different dose-dependent effect on Tregs, both in vivo and in vitro, resulting in particular in the acquisition of FOXP3 and CD39.Les cellules T CD4+ régulatrices (Treg) sont essentielles au maintien de la tolérance périphérique, la prévention des maladies auto-immunes comme la DM et jouent un rôle dans la réponse anti-tumorale et la prévention de la maladie du greffon contre l’hôte (graft versus host disease – GVHD), après allogreffe de moelle. Grâce à deux marqueurs associés au métabolisme de l’ATP, le CD26 et le CD39, et au marqueur de maturation CD45RA, nous avons séparé les Treg en 5 sous-populations distinctes, chacune représentant un stade de maturation différent. Les facteurs micro-environnementaux dictent cette maturation ainsi que les fonctions de ces différentes sous-populations. La DM est une maladie auto-immune affectant principalement la peau et le muscle. Au cours de cette pathologie, nous avons observé une modification phénotypique des Treg avec une diminution d’expression du CD25 et une accumulation de populations CD39+. L’étude de la polarisation immunitaire a révélé la disparition des cellules MAIT (mucosal-associated invariant T cells) circulantes, l’existence d’un profil lymphocytaire similaire entre la forme classique et la forme amyopathique et une polarisation cutanée « interféron de type I » importante au cours de la forme avec anticorps anti-MDA5 en lien avec la présence d’interféron kappa. Enfin, nous nous sommes intéressés à des patients présentant un SMD ou une LAM en rechute après allogreffe traités par azacytidine (AZA), un agent hypométhylant. Nous avons pu montrer que le phénotype des Treg était modifié par rapport à des individus non greffés mais qu’il ne différait pas entre rechuteurs et non rechuteurs. Le traitement par AZA semble exercer un effet sur les Treg différent en fonction de la dose, à la fois in vivo et in vitro, aboutissant notamment à l’acquisition du FOXP3 et du CD39.(MED - Sciences médicales) -- UCL, 202

Regulatory T lymphocytes and immune polarization : study applied to dermatomyositis and the context of myelodysplastic syndromes and acute myeloid leukemia in relapse after allogeneic transplantation

Les cellules T CD4+ régulatrices (Treg) sont essentielles au maintien de la tolérance périphérique, la prévention des maladies auto-immunes comme la DM et jouent un rôle dans la réponse anti-tumorale et la prévention de la maladie du greffon contre l’hôte (graft versus host disease – GVHD), après allogreffe de moelle. Grâce à deux marqueurs associés au métabolisme de l’ATP, le CD26 et le CD39, et au marqueur de maturation CD45RA, nous avons séparé les Treg en 5 sous-populations distinctes, chacune représentant un stade de maturation différent. Les facteurs microenvironnementaux dictent cette maturation ainsi que les fonctions de ces différentes sous-populations. La DM est une maladie auto-immune affectant principalement la peau et le muscle. Au cours de cette pathologie, nous avons observé une modification phénotypique des Treg avec une diminution d’expression du CD25 et une accumulation de populations CD39+. L’étude de la polarisation immunitaire a révélé la disparition des cellules MAIT (mucosal-associated invariant T cells) circulantes, l’existence d’un profil lymphocytaire similaire entre la forme classique et la forme amyopathique et une polarisation cutanée 4 « interféron de type I » importante au cours de la forme avec anticorps anti-MDA5 en lien avec la présence d’interféron kappa. Enfin, nous nous sommes intéressés à des patients présentant un SMD ou une LAM en rechute après allogreffe traités par azacytidine (AZA), un agent hypométhylant. Nous avons pu montrer que le phénotype des Treg était modifié par rapport à des individus non greffés mais qu’il ne différait pas entre rechuteurs et non rechuteurs. Le traitement par AZA semble exercer un effet sur les Treg différent en fonction de la dose, à la fois in vivo et in vitro, aboutissant notamment à l’acquisition du FOXP3 et du CD39.Regulatory CD4 + T cells (Treg) are essential for maintaining peripheral tolerance, preventing autoimmune diseases like dermatomyositis, and play a role in the anti-tumor response and prevention of graft versus host disease (graft versus host disease - GVHD) after allogeneic bone marrow transplantation. Using two markers associated with ATP metabolism, CD26 and CD39, and the CD45RA maturation marker, we separated the Treg into 5 distinct subpopulations, each representing a different stage of maturation. Micro-environmental factors dictate this maturation as well as the functions of these different sub-populations. Dermatomyositis is an autoimmune disease primarily affecting the skin and muscle. During this pathology, we observed a phenotypic modification of Treg with a decrease in CD25 expression and an accumulation of CD39+ populations. The study of immune polarization revealed the disappearance of circulating MAIT (mucosal-associated invariant T cells) cells, the existence of a similar lymphocyte profile between the classic form and the amyopathic form and a skin "type I interferon” polarization during anti-MDA5 associated with the presence of interferon kappa. Finally, we were interested in patients presenting with relapsing MDS or AML after allogeneic transplantation treated with azacytidine (AZA), a hypomethylating agent. We were able to show that the Treg phenotype was modified compared to ungrafted individuals, but that it did not differ between relapse and non-relapse. Treatment with AZA appears to have a different dose-dependent effect on Tregs, both in vivo and in vitro, resulting in particular in the acquisition of FOXP3 and CD39

Biomarkers in Adult Dermatomyositis: Tools to Help the Diagnosis and Predict the Clinical Outcome

International audienceDermatomyositis pathophysiology is complex. In recent years, medical research has identified molecules associated with disease activity. Besides providing insights into the driving mechanisms of dermatomyositis, these findings could provide potential biomarkers. Activity markers can be used to monitor disease activity in clinical trials and may also be useful in daily practice. This article reviews molecules that could be used as biomarkers for diagnosis and monitoring dermatomyositis disease activity

Histo-morphological description of the digestive system of the Rippon Barbel Barbus altianals (Boulenger 1900): A potential species for culture

Morphology of the digestive system can help define the feeding adaptation habits of a given fish species in a given environment. In a study to describe the nature and functionality of the digestive system of Barbus altianalis, samples of B. altianalis were taken from River Nile. Their Lengths and weights were measured and the gut structure preserved. The structure of the digestive tract of the B. altianalis was described using simple morphological observations and standard histological procedures. The digestive tube of B. altianalis is stomachless and valveless, progressively and uniformly reducing in size from the proximal to distal end. The digestive tract is on average 2.22 ± 0.37 times longer than its body length. The mouth is terminal and protrusible and pharyngeal palatal organ is well developed. The last gill arch is modified into pharyngeal teeth and the eosophagus is short and muscular. Histological sections revealed the presence of taste buds from the lips to the cranial eosophagus and these regions of the digestive tract are lined by a stratified squamous epithelium. The intestines are lined by simple or pseudo stratified columnar epithelial layer which is highly folded. Goblet cells containing both acidic and neutral mucins are present throughout the entire digestive tract and are more numerous in the pharynx and the proximal part of the intestine. Lobes of pancreatic acini are discrete and scattered among liver cells, around the intestine and few are seen in the spleen surrounding blood vessels. Thus, the liver could most accurately be termed a hepatopancreas structure.Key words: Goblet cells, hepatopancreas, intestine, mucin

Acropulpitis in systemic lupus erythematosus is associated with high type 1 interferon signature

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Increased CD8CD28 circulating T cells and high blood interferon score characterize the systemic inflammation of amyopathic dermatomyositis.

Amyopathic dermatomyositis (ADM) is a subtype of DM defined by the presence of cutaneous signs of DM with no evidence of muscle weakness or abnormal muscle enzymes for ≥ 6 months.1 Classical DM (CDM) is characterized by modification of circulating lymphocytes 4, type I interferon (IFN) signature 2, elevation of serum pro-inflammatory cytokines 3. Pathophysiology of ADM is less studied. We analysed circulating T cells by flowcytometry (using specific monoclonal antibodies), peripheral blood mononuclear cells type I IFN signature by PCR and serum cytokine levels by ELISA in a series of 17 ADM and 15 CDM patients. [...

Increased CD8+CD28- circulating T cells and high blood interferon score characterize the systemic inflammation of amyopathic dermatomyositis

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Increased CD8+CD28- circulating T cells and high blood interferon score characterize the systemic inflammation of amyopathic dermatomyositis

International audienceNo abstract availabl

Persistent deficiency of mucosal-associated invariant T cells during dermatomyositis.

OBJECTIVES: Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes that are important for antibacterial immunity and may have regulatory roles. MAIT cells are decreased during SLE. However, their frequencies and phenotype have not been investigated in DM. We studied MAIT cell frequencies and phenotype in DM patients with active and inactive disease (after treatment). METHODS: Peripheral blood flow cytometry analysis of MAIT cells was compared between DM (n = 22), SLE (n = 10), psoriasis (n = 7) and atopic dermatitis (n = 5) patients, and healthy controls (n = 19). RESULTS: A dramatic decrease of circulating MAIT cell frequency was observed in active DM and SLE patients compared with healthy controls and other inflammatory skin diseases [active DM: median = 0.25% (interquartile range 0.19-0.6%), P < 0.0001; active SLE: median = 0.61 (0.55-0.77), P < 0.0001 vs healthy controls: 2.32% (1.18-4.45%)]. MAIT cells from active DM patients had an abnormal phenotype including increased expression of CD25 and cytotoxic T-lymphocyte-associated protein 4 that correlated with their low frequency in the blood. CONCLUSION: In DM, peripheral blood MAIT cells are dramatically reduced and have an activated/exhausted phenotype that may be linked to increased activation-induced cell death