Advances in Neuroimmune Biology - Volume 5, issue 2

Authors: Adkins, Becky | Yoshimoto, Momoko

Article Type: Research Article

Abstract: In naïve adult CD4+ T cells, the Th2 locus, containing the Il5, Il13, and Il4 genes, is in a transcriptionally quiescent state. When naïve T cells differentiate into Th2 cells, the Th2 locus undergoes extensive epigenetic modifications which are permissive for gene expression. These modifications, which include the induction of DNase I hypersensitivity, permissive histone modifications, and DNA demethylation at CpG residues, are associated with Th2 differentiation and secretion of Th2 cytokines. Regulatory regions, such as the Il4 and Il13 promoters, the locus control region (LCR), and intra- and intergenic enhancers are the primary targets of these modifications. Unlike …adult animals, neonates are considered to be Th2 biased due to the robust development of Th2 lineage cells coupled with a deficiency in Th1 differentiation. This Th2 bias is reflected in the epigenetic status of the Th2 locus. In naïve neonatal CD4+ T cells in thymus and lymph nodes, key regulatory regions in the Th2 locus pre-exist in a hypomethylated state and these cells are already primed for Th2 status. Here, we focus on the epigenetic modifications in fetal and neonatal T cells and the association of the Th2 locus hypomethylated status with the characteristics of neonatal Th2 biased immunity. Show more

Keywords: Ontogeny of the immune system, Th2 locus, Epigenetic regulation, DNA methylation, Th2 cytokine gene expression

DOI: 10.3233/NIB-140078

Citation: Advances in Neuroimmune Biology, vol. 5, no. 2, pp. 69-73, 2014

Authors: Reyes-Lagos, José Javier | Echeverría-Arjonilla, Juan Carlos | Peña-Castillo, Miguel Ángel | Montiel-Castro, Augusto J. | Pacheco-López, Gustavo

Article Type: Research Article

Abstract: The precise mechanisms for the onset of labor at term remain unknown, yet several studies in humans reveal the role of cytokines in the initiation and maintenance of labor, showing many of the hallmarks of inflammation. Recent findings suggest a possible relationship between the activity of the autonomic nervous system (ANS) and the vagal anti-inflammatory response during labor. Furthermore, the role of vaginal microbiota is particularly important during pregnancy because vaginal dismicrobism is one of the most important mechanisms associated with preterm birth. In this review, we present evidence suggesting that a sterile anti-inflammatory response is manifested to attenuate the …excessive inflammation introduced by low-risk labor at term, involving either the action of a cholinergic pathway, uterine-like myokines or the vaginal microbiome. Show more

Keywords: Anti-inflammatory response, heart rate variability, vaginal microbiota, pregnancy, labor

DOI: 10.3233/NIB-140085

Citation: Advances in Neuroimmune Biology, vol. 5, no. 2, pp. 75-89, 2014

Authors: Lepletier, Ailin | Villar, Silvina Raquel | Pérez, Ana Rosa | Morrot, Alexandre | Savino, Wilson

Article Type: Research Article

Abstract: During stressful processes, for example infectious diseases, neuroendocrine and immune networks act multi-directionally facilitating the host response. However in exacerbated settings, this homeostatic mechanism may be lost. Recent findings unravelled an imbalance of the immunoneuroendocrine network during Chagas disease, the infection caused by the protozoan Trypanosoma cruzi. During the acute immune response against T. cruzi, inflammatory and neuroendocrine responses become dysregulated with harmful effects for the host. One target organ is the thymus. In acutely-infected mice, it undergoes a severe atrophy, with massive depletion of immature double positive CD4+ CD8+ (DP) thymocytes, which seems to be linked to a …systemic and intrathymic cytokine/hormonal imbalance, involving TNF-α, glucocorticoids and prolactin. In addition, there is an abnormal export of potentially autoreactive DP cells to the periphery of the immune system, which is apparently regulated by the prolactin levels. Furthermore, TNF-α is able to differentially modulate the hypothalamus-pituitary-adrenal (HPA) axis: while having stimulatory effects at the HP unit at the adrenal it is inhibitory. Interestingly, chronically infected humans with chagasic myocardiopathy also showed alterations in HPA axis. Understanding of how T. cruzi infection lead to neuroendocrine immune-associated disturbances will provide important clues to better dissect the mechanisms underlying the pathophysiology of Chagas disease. Show more

Keywords: Hormonal circuitry, Chagas disease, thymus atrophy, double positive T cells, lymph nodes

DOI: 10.3233/NIB-140094

Citation: Advances in Neuroimmune Biology, vol. 5, no. 2, pp. 91-98, 2014

Authors: Loria, Roger M. | Luna-Nophal, Angélica | Muňiz-Henández, Saé | Morales-Montor, Jorge

Article Type: Research Article

Abstract: Carriers of the tapeworm Taenia solium are the main risk factor in the transmission of both human neurocysticercosis and porcine cysticercosis. One quarter of the world's human population is exposed to intestinal helminthic parasites; consequently, agents that can eliminate and/or reduce the incidence of carriers could significantly enhance human and animal health. Neurosteroid hormones up regulate host resistance to infections by viruses, bacteria and parasites. An analogue (LMM102) devoid of androgenic or estrogenic activity was tested in vitro and in vivo for its ability to modulate T. solium reproduction, growth, viability, and infectivity. Three groups of female adult hamsters (Mesocricetus …auratus) were tested; the first were injected subcutaneously (SC) with 2 mg/kg of LMM102, while the other two served as vehicles and untreated control groups, respectively. After two weeks, all animals were orally infected with 4 viable T. solium cysticerci. At 2 weeks post infection, LMM102 -treated hamsters showed an 80% reduction in adult worm recovery with a 75% reduced length as compared to either vehicle or untreated infected controls. Only in LMM102 treated, infected animals, spleen and mesenteric lymph nodes were increased with 5-fold elevation of leukocyte proliferation. Duodenal mucosa cytokine IL-4, IL-6 and TNF-α were also elevated. These results show that LMM102 protects hamsters from T. solium adult tapeworm establishment by improving intestinal mucosal immunity, suggesting the potential use of this hormone analogue as novel enhancer of the gut immune response against intestinal helminthic infections and other gastrointestinal tract-related disorders. Show more

Keywords: Neurosteroids, DHEA analog: Host resistance, T. solium

DOI: 10.3233/NIB-140095

Citation: Advances in Neuroimmune Biology, vol. 5, no. 2, pp. 99-107, 2014

Authors: Nava-Castro, Karen E. | Palacios-Arreola, Margarita I. | Ostoa-Saloma, Pedro | Muñiz-Hernández, Saé | Cerbón, Marco A. | Gomez-Icazbalceta, Guillermo | Muñoz-Cruz, Samira | Aguilar-Díaz, Hugo | Pavón, Lenin | Castro-Romero, Julieta Ivone | Morales-Montor, Jorge

Article Type: Research Article

Abstract: Breast cancer is a disease in which abnormal cell proliferation leads to uncontrolled growth of breast tissue. Breast cancer can start in various areas of the breast, such as the ducts, lobes, and, in some cases, the intervening tissue. For many years, inflammatory infiltrates in tumors have been suggested to reflect the origin of cancer; however, little is known about the function of chronic inflammation in malignant transformation. Sex hormones are associated with many types of cancer, such as colon, cervical, and especially breast. Estrogen-dependent breast cancer (EDBC) constitutes approximately 50% to 80% of all cases of breast cancer. Furthermore, …estrogen-dependency is linked to the initiation of malignancy by promoting the growth and proliferation of mammary cells and it is related to prognosis and treatment. The correlation between sex hormones and breast cancer has been recognized for decades, but the mechanisms of this association remain unknown. In recent years, a more enriched landscape of this relationship has emerged. Intervention by the immune system in cancer begins with the detection of transformed cells and their proliferation—not with the defense and effort to restrain an established tumoral mass. In the late 1950s, Burnet introduced the immunosurveillance theory, which proposes that immune system cells detect and attack transformed cells, eliciting an adaptive response that succeeds and eliminates them or fails, leading to the formation of a tumoral mass and cancer onset. Conversely, sex hormones are important modulators of the immune system. Growing evidence demonstrates a reciprocal relationship between sex steroids and the immune system. Because the innate immune response determines the type of adaptive immunity that develops, hormonal effects on the former can affect adaptive responses. The sex steroids estrogens, progesterone, and testosterone regulate the growth, differentiation, survival, and function of many cell types that mediate homeostasis, immunity, and breast cancer. The presence of sex steroid receptors on immune cells indicates that sex steroids exert their effects by binding to them. Sex steroids and immunity are inextricably linked, and their mutual regulation influences the maintenance of the immune balance. Understanding the mechanisms of action of sex steroids on immune cells is paramount to developing novel therapies for chronic diseases that are associated to immune dysregulation, such as breast cancer. This chapter describes the risk factors in breast cancer, the hormonal factors that are involved, the immunological response toward cancer, and the effects of sex steroids on immune system cells and their implications for the incidence of breast cancer. Show more

Keywords: Breast cancer, sex steroids, immune response, immunoendocrine network

DOI: 10.3233/NIB-140097

Citation: Advances in Neuroimmune Biology, vol. 5, no. 2, pp. 109-131, 2014