ABSTRACT
INTRODUCTION: The prevalence of peanut allergy (PA) has increased, affecting approximately 1.1% of children in Western countries. PA causes life-threatening anaphylaxis and frequently persists for life. There are no standardized curative therapies for PA, and avoidance of peanuts remains the main therapeutic option. A better understanding of the pathogenesis of PA is essential to identify new treatment strategies. Intestinal dendritic cells (DCs) are essential in the induction and maintenance of food tolerance because they present dietary allergens to T cells, thereby directing subsequent immune responses. Areas covered: In this review, we discuss the factors related to the acquisition of oral tolerance to peanut proteins. We focus on intestinal DC-related aspects, including the latest advances in the biology of intestinal DC subtypes, effect of tolerance-inducing factors on DCs, effect of dietary components on oral tolerance, and role of DCs in peanut sensitization. Expert commentary: Given the increasing prevalence of PA, difficulty of avoiding peanut products, and the potentially serious accidental reactions, the development of novel therapies for PA is needed. The ability of DCs to trigger tolerance or immunity makes them an interesting target for new treatment strategies against PA.
Subject(s)
Allergens/immunology , Antigen Presentation , Dendritic Cells/immunology , Intestinal Mucosa/immunology , Peanut Hypersensitivity/immunology , T-Lymphocytes/immunology , Child , Child, Preschool , Dendritic Cells/pathology , Female , Humans , Intestinal Mucosa/pathology , Male , Peanut Hypersensitivity/epidemiology , Peanut Hypersensitivity/pathology , Prevalence , T-Lymphocytes/pathologyABSTRACT
Hypothyroxinemia (Hpx) is a highly frequent condition characterized by low thyroxine (T4) and normal 3,3',5'-triiodothyronine (T3) and thyroid stimulating hormone (TSH) levels in the blood. Gestational Hpx is closely related to cognitive impairment in the human offspring. In animal models gestational Hpx causes impairment at glutamatergic synapsis, spatial learning, and the susceptibility to suffer strong autoimmune diseases like experimental autoimmune encephalomyelitis (EAE). However, the mechanisms underlying these phenotypes are unknown. On the other hand, it has been shown that astrocytes and microglia affect the outcome of EAE. In fact, the activation of astrocytes and microglia in the central nervous system (CNS) contributes to EAE progression. Thus, in this work, the reactivity of astrocytes and microglia from rats gestated in Hpx was evaluated aiming to understand whether these cells are targets of gestational Hpx. Interestingly, microglia derived from the offspring gestated in Hpx were less reactive compared to microglia derived from offspring gestated in euthyroidism. Instead, astrocytes derived from the offspring gestated in Hpx were significantly more reactive than the astrocytes from the offspring gestated in euthyroidism. This work contributes with novel information regarding the effects of gestational Hpx over astrocytes and microglia in the offspring. It suggests that astrocyte could react strongly to an inflammatory insult inducing neuronal death in the CNS.
Subject(s)
Astrocytes/pathology , Inflammation/blood , Inflammation/pathology , Microglia/pathology , Thyroxine/blood , Animals , Apoptosis/drug effects , Astrocytes/drug effects , Astrocytes/metabolism , Cells, Cultured , Chemokine CXCL2/metabolism , Female , Glial Fibrillary Acidic Protein/metabolism , Interleukin-1beta/metabolism , Male , Microglia/drug effects , Microglia/metabolism , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/metabolism , Pregnancy , Rats, Sprague-Dawley , Tissue Inhibitor of Metalloproteinase-1/metabolism , Tumor Necrosis Factor-alpha/pharmacologyABSTRACT
Thyroid hormones (THs) during pregnancy contribute significantly to cellular differentiation and development in several tissues of the offspring, principally the central nervous system (CNS). TH deficiencies, such as hypothyroidism or hypothyroxinemia, are highly frequent during pregnancy worldwide and known to be detrimental for the development of the fetus. The function of CNS in the offspring gestated under TH deficiency will be irreversible impaired, causing low intellectual quotient, attention deficit, and mental retardation. On the other hand, little is known about the effects of TH deficiency in the offspring immune system, being the prevalent notion that the effects are reversible and only for a while will affect the number of B and T cells. Recent studies have shown that maternal hypothyroidism can altered the function of immune system in the offspring, rendering the female offspring more susceptible to suffer autoimmune-inflammatory diseases, such as experimental autoimmune encephalomyelitis (EAE) and to be more resistant to a bacterial infection. In this article we discuss these recent findings, as well as the possible mechanisms underlying these effects and the potential implications for human health.