Role of Regulatory Cells in Oral Tolerance

Wawrzyniak, Marcin; O’Mahony, Liam; Akdiş, Mübeccel

doi:10.4168/aair.2017.9.2.107

Cited by 62 publications

(41 citation statements)

References 77 publications

(75 reference statements)

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“…Actually, a higher number of circulating Treg cells was evidenced in children who had outgrown cow's milk allergy (CMA) compared to children who had an active CMA, and the development of clinical tolerance to CM was associated with higher number of circulating Treg cells . This thus suggests that not only the maintenance but also the development of oral tolerance against food antigens requires Treg cells, although other cells may also be involved …”

Section: Introductionmentioning

confidence: 99%

“…5 This thus suggests that not only the maintenance but also the development of oral tolerance against food antigens requires Treg cells, although other cells may also be involved. 3 Cow's milk allergy is one of the most common FAs observed in early childhood, with an estimated incidence ranging between 2% and 3%. 6 Although recent studies demonstrated an increasing frequency of non-IgE-mediated CMA, 7 IgE-mediated CMA is still found in more than 50% of the CM-allergic patients.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of the efficiency of hydrolyzed whey formula to prevent cow’s milk allergy in the BALB/c mouse model

Chikhi

Elmecherfi

Bernard

et al. 2019

Pediatric Allergy Immunology

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Background Partially hydrolyzed milk formulas have been proposed for primary prevention in at‐risk infants, but evidence of their efficiency and elucidation of the underlying mechanisms are still lacking. Thanks to a Th2‐biased mouse model mimicking at‐risk patients, we aimed to assess the potency of a partially hydrolyzed whey formula (pHWF) to induce oral tolerance thus preventing further cow's milk (CM) allergy. Methods BALB/c mice were gavaged with pHWF, standard milk formula (SF), or vehicle only (PBS+). All mice were then orally sensitized to CM using cholera toxin and further chronically exposed to CM. Humoral (IgE, IgG1, IgG2a) and cellular (Th2/Th1/Th17 cytokine secretion; frequency of CD4+GATA3+ and CD4+CD25+Foxp3+ T cells in the spleen) responses against β‐lactoglobulin (BLG) and whole caseins (CAS) were assessed, as well as a marker of elicitation of allergic reaction (mMCP‐1) released after an oral challenge with CM. Results All markers of sensitization and of allergic reaction were evidenced in the PBS+ mice and were significantly enhanced upon chronic exposure. Gavage with SF totally and durably prevented sensitization and elicitation of the allergic reaction. Conversely, pre‐treatment with pHWF only reduced BLG‐specific sensitization (IgE, Th2 cytokines), with no significant effect on sensitization to caseins. However, pHWF pre‐treatment significantly reduced mMCP‐1 concentration in plasma after CM challenges. CD4+CD25+Foxp3+ Treg cell frequency could not be correlated with tolerance efficiency. Conclusion Partially hydrolyzed whey formula only partially prevents the further development of CM allergy in this Th2‐biased model. A hydrolysate from both whey and casein fractions may be more efficient.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Evaluation of the efficiency of hydrolyzed whey formula to prevent cow’s milk allergy in the BALB/c mouse model

Chikhi

Elmecherfi

Bernard

et al. 2019

Pediatric Allergy Immunology

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“…Tregs can support the reduction of allergic diseases, and, on the other hand, the progression of cancer . Multiple mechanisms are employed by Treg cells and include production of inhibitory cytokines (IL‐10, TGF‐β, and IL‐35), cytolysis of effector T cells and APCs (via granzymes A and B), direct inhibition of DCs (eg, via PD‐1 and CTLA4) and metabolic disruption of effector cells (CD25, cAMP, adenosine, CD39, and CD73) . Germ‐free mice do not fully develop Tregs, similarly to mice treated with antibiotics or mice lacking Toll‐like receptors (TLRs).…”

Section: Microbiota Regulating Cellular Players In Innate and Adaptivmentioning

confidence: 99%

AllergoOncology: Microbiota in allergy and cancer—A European Academy for Allergy and Clinical Immunology position paper

Untersmayr

Bax

Bergmann³

et al. 2019

Allergy

Self Cite

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The microbiota can play important roles in the development of human immunity and the establishment of immune homeostasis. Lifestyle factors including diet, hygiene, and exposure to viruses or bacteria, and medical interventions with antibiotics or anti‐ulcer medications, regulate phylogenetic variability and the quality of cross talk between innate and adaptive immune cells via mucosal and skin epithelia. More recently, microbiota and their composition have been linked to protective effects for health. Imbalance, however, has been linked to immune‐related diseases such as allergy and cancer, characterized by impaired, or exaggerated immune tolerance, respectively. In this AllergoOncology position paper, we focus on the increasing evidence defining the microbiota composition as a key determinant of immunity and immune tolerance, linked to the risk for the development of allergic and malignant diseases. We discuss novel insights into the role of microbiota in disease and patient responses to treatments in cancer and in allergy. These may highlight opportunities to improve patient outcomes with medical interventions supported through a restored microbiome.

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“…L'ensemble de ces éléments permettrait la conversion des lymphocytes T naïfs en T régulateurs périphériques CD4 + CD25 + FoxP3 et leur homing dans la muqueuse intestinale. Ces lymphocytes seraient ensuite eux-mêmes impliqués dans l'inhibition des réponses Th2 et IgE spécifiques aux antigènes alimentaires, et dans la promotion des réponses IgG4 [6]. Une perturbation du fonctionnement des cellules dendritiques pourra ainsi rompre l'équilibre délicat immunité vs tolérance, générant l'apparition d'une réponse de type Th2 et d'une hypersensibilité aux allergènes alimentaires [7].…”

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Rôle des cellules dendritiques de la muqueuse digestive dans la tolérance orale

Evrard

2017

Revue Française d'Allergologie

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Le système immunitaire de la muqueuse digestive, communément appelé le Gut-Associated Lymphoid Tissu (GALT), est exposé en permanence à de très nombreux antigènes étrangers provenant simultanément de l'alimentation et des micro-organismes de la flore commensale intestinale. Parallè-lement à cela, l'intestin représente une des principales portes d'entrée dans l'organisme des micro-organismes pathogènes. Le GALT est donc soumis à un challenge difficile, car il doit tolérer les antigènes alimentaires ou commensaux, inoffensifs voire bénéfiques, tout en restant capable de détecter et d'éliminer les antigènes issus de micro-organismes dangereux [1]. Au sein de cette muqueuse, les cellules dendritiques, véritables sentinelles de l'immunité, jouent un rôle crucial en orchestrant les réponses immunitaires innées et adaptatives, et en gouvernant en permanence le choix entre tolérance ou immunité. Néan-moins, il apparaît de plus en plus nettement que le tube digestif constitue un environnement trop complexe pour qu'une seule population cellulaire contrôle l'ensemble des types de réponses immunitaires potentielles et soit capable de les adapter finement aux diverses natures des antigènes rencontrés. Il est donc maintenant admis que ce contexte physiologique particulier a conduit au cours de l'évolution à l'apparition de différentes populations spécialisées de phagocytes mononucléés, à la fois * Correspondance.Adresse e-mail : bevrard@chu-clermontferrand.fr des cellules dendritiques et des macrophages [2]. Les cellules dendritiques intestinales constituent ainsi un ensemble de sous-populations hétérogènes exprimant de façon différen-tielle un certain nombre de marqueurs phénotypiques, dont CD103, CD11b, CD172a/SIRP␣ et CX3CR1 [3]. Ces souspopulations ont des caractéristiques fonctionnelles différentes qui commencent à être de mieux en mieux appréhendées. Certaines en particulier seraient fondamentales dans la mise en place de la tolérance orale aux antigènes alimentaires, principalement les cellules dendritiques migratrices CD103 + CD11b − et dans une moindre mesure CD103 + CD11b + [4,5]. En effet, en condition homéostasique, après migration de la Lamina propria vers les ganglions lymphatiques mésentériques, ces cellules présentent la capacité de produire de l'acide rétinoïque grâce à une enzyme, la retinaldehyde dehydrogenase 2 (RALDH2), ainsi que du TGF-␤ et expriment l'indoléamine 2,3-dioxygénase (IDO). L'ensemble de ces éléments permettrait la conversion des lymphocytes T naïfs en T régulateurs périphériques CD4 + CD25 + FoxP3 et leur homing dans la muqueuse intestinale. Ces lymphocytes seraient ensuite eux-mêmes impliqués dans l'inhibition des réponses Th2 et IgE spécifiques aux antigènes alimentaires, et dans la promotion des réponses IgG4 [6]. Une perturbation du fonctionnement des cellules dendritiques pourra ainsi rompre l'équilibre délicat immunité vs tolérance, générant l'apparition d'une réponse de type Th2 et d'une hypersensibilité aux allergènes alimentaires [7]. Dès lors, cibler plus finement les rôles de cha...

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Role of Regulatory Cells in Oral Tolerance

Cited by 62 publications

References 77 publications

Evaluation of the efficiency of hydrolyzed whey formula to prevent cow’s milk allergy in the BALB/c mouse model

Evaluation of the efficiency of hydrolyzed whey formula to prevent cow’s milk allergy in the BALB/c mouse model

AllergoOncology: Microbiota in allergy and cancer—A European Academy for Allergy and Clinical Immunology position paper

Rôle des cellules dendritiques de la muqueuse digestive dans la tolérance orale

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