Regulatory T Cells Developing Peri-Weaning Are Continually Required to Restrain Th2 Systemic Responses Later in Life

Knoop, Kathryn A.; McDonald, Keely G.; Hsieh, Chyi Song; Tarr, Phillip I.; Newberry, Rodney D.

doi:10.3389/fimmu.2020.603059

Cited by 15 publications

(13 citation statements)

References 59 publications

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“…Before weaning, the maternal breastmilk proteins constitute the majority of luminal antigens contributing to colonic pTregs generation. Colonic Treg from such origin plays an important role in tolerance maintenance and allergy suppression by dampening the Th2 responses ( 67 , 68 ). Unlike Tregs in the colon, Tregs in the small intestine lamina propria are induced during weaning when exposure to solid food commences.…”

Section: Impact Of Diet On Treg Developmentmentioning

confidence: 99%

Your Regulatory T Cells Are What You Eat: How Diet and Gut Microbiota Affect Regulatory T Cell Development

et al. 2022

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Modern industrial practices have transformed the human diet over the last century, increasing the consumption of processed foods. Dietary imbalance of macro- and micro-nutrients and excessive caloric intake represent significant risk factors for various inflammatory disorders. Increased ingestion of food additives, residual contaminants from agricultural practices, food processing, and packaging can also contribute deleteriously to disease development. One common hallmark of inflammatory disorders, such as autoimmunity and allergies, is the defect in anti-inflammatory regulatory T cell (Treg) development and/or function. Treg represent a highly heterogeneous population of immunosuppressive immune cells contributing to peripheral tolerance. Tregs either develop in the thymus from autoreactive thymocytes, or in the periphery, from naïve CD4+ T cells, in response to environmental antigens and cues. Accumulating evidence demonstrates that various dietary factors can directly regulate Treg development. These dietary factors can also indirectly modulate Treg differentiation by altering the gut microbiota composition and thus the production of bacterial metabolites. This review provides an overview of Treg ontogeny, both thymic and peripherally differentiated, and highlights how diet and gut microbiota can regulate Treg development and function.

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Section: Impact Of Diet On Treg Developmentmentioning

confidence: 99%

Your Regulatory T Cells Are What You Eat: How Diet and Gut Microbiota Affect Regulatory T Cell Development

et al. 2022

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“…Interestingly, Al Nabhani et al showed that these microbiota-induced RORγt + Tregs must be generated during the weaning reaction in order to prevent pathological imprinting of the immune system ( 128 ), e.g. to prevent spontaneous Th2-mediated allergic responses to dietary antigens ( 131 ) and protect from dextran sodium sulfate (DSS)-mediated severe colitis in mice ( 132 ). Regarding humans, the knowledge is still very limited.…”

Section: Tissue-resident Tregs: Qualitative and Quantitative Changesmentioning

confidence: 99%

The dark side of Tregs during aging

et al. 2022

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In the last century, we have seen a dramatic rise in the number of older persons globally, a trend known as the grey (or silver) tsunami. People live markedly longer than their predecessors worldwide, due to remarkable changes in their lifestyle and in progresses made by modern medicine. However, the older we become, the more susceptible we are to a series of age-related pathologies, including infections, cancers, autoimmune diseases, and multi-morbidities. Therefore, a key challenge for our modern societies is how to cope with this fragile portion of the population, so that everybody could have the opportunity to live a long and healthy life. From a holistic point of view, aging results from the progressive decline of various systems. Among them, the distinctive age-dependent changes in the immune system contribute to the enhanced frailty of the elderly. One of these affects a population of lymphocytes, known as regulatory T cells (Tregs), as accumulating evidence suggest that there is a significant increase in the frequency of these cells in secondary lymphoid organs (SLOs) of aged animals. Although there are still discrepancies in the literature about modifications to their functional properties during aging, mounting evidence suggests a detrimental role for Tregs in the elderly in the context of bacterial and viral infections by suppressing immune responses against non-self-antigens. Interestingly, Tregs seem to also contribute to the reduced effectiveness of immunizations against many pathogens by limiting the production of vaccine-induced protective antibodies. In this review, we will analyze the current state of understandings about the role of Tregs in acute and chronic infections as well as in vaccination response in both humans and mice. Lastly, we provide an overview of current strategies for Treg modulation with potential future applications to improve the effectiveness of vaccines in older individuals.

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“…As such, preweaning induction of colonic GAP triggers the activation of T cells and preferential development of Tregs specific for bacterial antigens in the colon‐draining MLNs followed by their migration in the colon LP where they establish tolerance to the microbiota [31]. Around weaning, the detection of the increased bacterial load by colonic goblet cells via a Myd88‐dependant pathway inhibits colonic GAPs whereas small intestinal GAPs start to form, are maintained throughout life, and by contrast play a key role in the tolerance to food antigens [180,181] (Fig. 3).…”

Section: Early‐life Defense Mechanisms and Immune Responsesmentioning

confidence: 99%

Spatial and temporal key steps in early‐life intestinal immune system development and education

et al. 2021

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Education of our intestinal immune system early in life strongly influences adult health. This education strongly relies on series of events that must occur in well-defined time windows. From initial colonization by maternalderived microbiota during delivery to dietary changes from mother's milk to solid foods at weaning, these early-life events have indeed long-standing consequences on our immunity, facilitating tolerance to environmental exposures or, on the contrary, increasing the risk of developing noncommunicable diseases such as allergies, asthma, obesity, and inflammatory bowel diseases. In this review, we provide an outline of the recent advances in our understanding of these events and how they are mechanistically related to intestinal immunity development and education. First, we review the susceptibility of neonates to infections and inflammatory diseases, related to their immune system and microbiota changes. Then, we highlight the maternal factors involved in protection and education of the mucosal immune system of the offspring, the role of the microbiota, and the nature of neonatal immune system until weaning. We also present how the development of some immune responses is intertwined in temporal and spatial windows of opportunity. Finally, we discuss pending questions regarding the neonate particular immune status and the activation of the intestinal immune system at weaning.

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Regulatory T Cells Developing Peri-Weaning Are Continually Required to Restrain Th2 Systemic Responses Later in Life

Cited by 15 publications

References 59 publications

Your Regulatory T Cells Are What You Eat: How Diet and Gut Microbiota Affect Regulatory T Cell Development

Your Regulatory T Cells Are What You Eat: How Diet and Gut Microbiota Affect Regulatory T Cell Development

The dark side of Tregs during aging

Spatial and temporal key steps in early‐life intestinal immune system development and education

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