Hsp65-producing Lactococcus lactis inhibits experimental autoimmune encephalomyelitis by preventing cell migration into spinal cord.

Multiple sclerosis is an autoimmune disease that affects the central nervous system. Because of its complexity and the difficulty to treat, searching for immunoregulatory responses that reduce the clinical signs of disease by non-aggressive mechanisms and without adverse effects is a scientific challenge. Herein we propose a protocol of oral tolerance induction that prevented and controlled MOG-induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. The genetically modified strain HSP65-producing Lactococcus lactis was orally administered for 5 consecutive days either before or during disease development in mice. Both protocols of feeding HSP65 resulted in significant reduction in the clinical score of EAE. Frequencies of LAP+CD4+Foxp3- regulatory T cells were higher in spleens and inguinal lymph nodes of fed mice. In addition, intravital microscopy showed that adherence of leukocytes to venules in the spinal cord was reduced in orally treated mice. Oral treatment with HSP65-producing L.lactis prevented leukocytes to leave the secondary lymphoid organs, therefore they could not reach the central nervous system. Despite the inhibition of pathological immune response that drive EAE development, activated T cells were at normal frequencies suggesting that oral tolerance did not induce general immunosuppression, but it led to specific control of pathogenic T cells. Our results indicate a novel therapeutic strategy to prevent and control autoimmune diseases such as multiple sclerosis.

Genetic spectrum, retinal phenotype, and peripapillary RNFL thickness in RPGR heterozygotes.

PURPOSE: Phenotypic heterogeneity with variable severity has been reported in female carriers of retinitis pigmentosa GTPase regulator (RPGR) mutations, including a male-type phenotype. A phenomenon not fully understood is peripapillary retinal nerve fiber layer (pRNFL) thickening in male patients with RPGR-associated X-linked retinitis pigmentosa, especially in the temporal sector. We aim to describe the genetic spectrum, retinal phenotypes, and pRNFL thickness in a cohort of Caucasian RPGR-mutation heterozygotes. METHODS: A cross-sectional study was conducted at an inherited retinal degeneration (IRD) reference center in Portugal. Female patients heterozygous for clinically significant RPGR variants were identified using the IRD-PT registry. A complete ophthalmologic examination was performed, complemented by macular and peripapillary spectral domain optical coherence tomography (SD-OCT), ultra-widefield color fundus photography (UW-CFP), and ultra-widefield fundus autofluorescence (UW-FAF). The retinal phenotypes were graded according to previously described classifications. The pRNFL thickness across the superior, inferior, nasal, and temporal quadrants was compared to the Spectralis® RNFL age-adjusted reference database. RESULTS: Forty-eight eyes from 24 females (10 families) were included in the study. Genetic analysis yielded 8 distinct clinically significant frameshift variants in RPGR gene, 3 of which herein reported for the first time. No association was found between mutation location and best-corrected visual acuity (BCVA) or retinal phenotype. Age was associated with worse BCVA and more advanced phenotypes on SD-OCT, UW-CFP, and UW-FAF. Seven women (29.17%) presented a male-type phenotype on UW-FAF in at least one eye. An association was found between UW-FAF and pRNFL thickness in the temporal sector (p = 0.003), with the most advanced fundus autofluorescence phenotypes showing increased pRNFL thickness in this sector. CONCLUSION: This study expands the genetic landscape of RPGR-associated disease by reporting 3 novel clinically significant variants. We have shown that clinically severe phenotypes are not uncommon among female carriers. Furthermore, we provide novel insights into pRNFL changes observed in RPGR heterozygotes that mimic what has been reported in male patients.

Genetic Background Affects the Mucosal Secretory IgA Levels, Parasite Burden, Lung Inflammation, and Mouse Susceptibility to Ascaris suum Infection.

Ascariasis is a neglected tropical disease that is widespread in the world and has important socioeconomic impacts. The presence of various stages of worm development in the pulmonary and intestinal mucosae induces a humoral and cellular immune response. However, although there is much evidence of the protective role of mucosal immunity against various pathogens, including helminths, there is still a gap in the knowledge about the immune response and the mechanisms of action that are involved in protection against diseases, especially in the initial phase of ascariasis. Thus, the aim of this study was to evaluate the kinetic aspects of the immune parasitological parameters in intestinal and pulmonary mucosae in male mice with early ascariasis. Therefore, two mouse strains that showed different susceptibilities to ascariasis (BALB/c and C57BL/6J) when experimentally infected with 2,500 infective eggs of Ascaris suum from time point 0 were examined: the immune parasitological parameters were evaluated each 2 days after infection over a period of 12 days. The results were suggestive of a synergetic action of intestinal and pulmonary secretory IgA (S-IgA) contributing to protection against early ascariasis by reducing the amount of migrating larvae as well as the influx of leukocytes in the lung and the consequent impairment of pulmonary capacity.

The influence of personality on the quality of vision after multifocal intraocular lens implantation.

OBJECTIVE: To assess the possible correlation between patients' personality traits and subjective perception of quality of vision (QoV), after multifocal intraocular lens (mIOL) implantation. METHODS: patients who had bilateral implantation of a non-diffractive X-WAVE or a trifocal lens were assessed 6 months postoperatively. Patients answered the NEO-Five Factor Inventory (NEO-FFI-20) questionnaire ("Big Five five-factor personality model") to examine their personality. Six months following surgery, patients were asked to fill a QoV questionnaire where they graded the frequency of 10 common visual symptoms. Primary outcomes were to evaluate the correlation between personality scores and the reported frequency of visual disturbances. RESULTS: The study comprised 20 patients submitted to bilateral cataract surgery, 10 with a non-diffractive X-WAVE lens (AcrySof® IQ Vivity) and 10 with a trifocal lens (AcrySof® IQ PanOptix). Mean age was 60.23 (7.06) years. Six months following surgery, patients with lower scores of conscientiousness and extroversion reported a higher frequency of visual disturbances (blurred vision, P = .015 and P = .009, seeing double images P = .018 and P = .006, and having difficulties focusing, P = .027 and P = .022, respectively). In addition, patients with high neuroticism scores had more difficulty focusing (P = .033). CONCLUSIONS: In this study, personality traits such as low conscientiousness and extroversion and high neuroticism significantly influenced QoV perception 6 months after bilateral multifocal lens implantation. Patients' personality questionnaires could be a useful preoperative assessment test to a mIOL.

Dynamic changes in B cell subpopulations in response to triple-negative breast cancer development.

Despite presenting a worse prognosis and being associated with highly aggressive tumors, triple-negative breast cancer (TNBC) is characterized by the higher frequency of tumor-infiltrating lymphocytes, which have been implicated in better overall survival and response to therapy. Though recent studies have reported the capacity of B lymphocytes to recognize overly-expressed normal proteins, and tumor-associated antigens, how tumor development potentially modifies B cell response is yet to be elucidated. Our findings reveal distinct effects of 4T1 and E0771 murine tumor development on B cells in secondary lymphoid organs. Notably, we observe a significant expansion of total B cells and plasma cells in the tumor-draining lymph nodes (tDLNs) as early as 7 days after tumor challenge in both murine models, whereas changes in the spleen are less pronounced. Surprisingly, within the tumor microenvironment (TME) of both models, we detect distinct B cell subpopulations, but tumor development does not appear to cause major alterations in their frequency over time. Furthermore, our investigation into B cell regulatory phenotypes highlights that the B10 Breg phenotype remains unaffected in the evaluated tissues. Most importantly, we identified an increase in CD19 + LAG-3 + cells in tDLNs of both murine models. Interestingly, although CD19 + LAG-3 + cells represent a minor subset of total B cells (< 3%) in all evaluated tissues, most of these cells exhibit elevated expression of IgD, suggesting that LAG-3 may serve as an activation marker for B cells. Corroborating with these findings, we detected distinct cell cycle and proliferation genes alongside LAG-3 analyzing scRNA-Seq data from a cohort of TNBC patients. More importantly, our study suggests that the presence of LAG-3 B cells in breast tumors could be associated with a good prognosis, as patients with higher levels of LAG-3 B cell transcripts had a longer progression-free interval (PFI). This novel insight could pave the way for targeted therapies that harness the unique properties of LAG-3 + B cells, potentially offering new avenues for improving patient outcomes in TNBC. Further research is warranted to unravel the mechanistic pathways of these cells and to validate their prognostic value in larger, diverse patient cohorts.

Surgical Management of Bilateral Limbal Stem Cell Deficiency.

At the age of 43 years-old, a man was left with bilateral limbal stem cell deficiency after an ocular alkaline burn with lime, which resulted in corneal opacification. After multiple unsuccessful surgical attempts to restore vision, including penetrating keratoplasties and Boston keratoprosthesis, visual acuity was counting fingers in the left eye. At 73 years of age, the patient underwent another surgery in his left eye. Cauterization of neovessels and removal of the vascular pannus were followed by partial excision of Tenon's capsule. Penetrating keratoplasty was followed by an intrastromal injection of anti-VEGF (vascular endothelial growth factor), and the ocular surface was covered with amniotic membrane. Postoperatively, the graft was clear with no signs of inflammation; vision improved to 20/50 and remained stable throughout the following two years. Herein we describe some adjunctive procedures that might have delayed failure and rejection of the corneal graft. This case demonstrates the difficulties in treating bilateral limbal stem cell deficiency in a tertiary eye care center with no capacity to perform stem cell therapy.

Comparison of outcomes between cross-linking plus topoguided excimer laser ablation and intrastromal corneal ring segments for keratoconus.

OBJECTIVE: To compare cross-linking (CXL) plus topography-guided photorefractive keratectomy (t-PRK) and intrastromal corneal ring segments (ICRS) in keratoconus patients, at 12 months of follow-up. METHODS: This was a longitudinal, retrospective multi-center study. We included a referred sample of 154 eyes from 149 patients with grade I-III Amsler-Krümeich keratoconus with insufficient corrected-distance visual acuity (CDVA). In group 1 (CXL plus t-PRK, 87 eyes), another possible indication for surgery was evidence of progression. Group 2 (ICRS, 67 eyes) included only eyes with paracentral keratoconus (thinnest point at the inferotemporal quadrant) with coincident axes, and evidence of stabilization was required. A subgroup analysis was performed regarding the disease topographic phenotype. At 12 months postoperatively, visual, refractive, and topographic outcomes were evaluated. RESULTS: Comparison of the outcomes between CXL plus t-PRK (group 1) and ICRS (group 2) showed similar improvements in CDVA (in group 1, CDVA improved 0.18 logMAR, and in group 2 0.12 logMAR, P = .18) and K2 (-2,45 [6.46] D in group 1 and -2.13 [1.67] D in group 2, P = .34) The improvement in cylinder power was greater in group 2 (-2.37 [2.07] D in group 2 versus -1.18 [2.63] D in group 1, P = .003); group 1 had a higher decrease in Kmax (- 3.26 [3.64] versus-1.74 [2.67], P = .001). CONCLUSIONS: Both CXL plus t-PRK and ICRS were equally effective in improving CDVA and topographic parameters in a similar group of keratoconus patients at 12 months.

Obesity-induced hyperglycemia impairs oral tolerance induction and aggravates food allergy.

Obesity and type 2 diabetes (T2D) have been found to be associated with abnormalities in several organs, including the intestine. These conditions can lead to changes in gut homeostasis, compromising tolerance to luminal antigens and increasing susceptibility to food allergies. The underlying mechanisms for this phenomenon are not yet fully understood. In this study, we investigated changes in the intestinal mucosa of diet-induced obese mice and found that they exhibited increased gut permeability and reduced Treg cells frequency. Upon oral treatment with ovalbumin (OVA), obese mice failed to develop oral tolerance. However, hyperglycemia treatment improved intestinal permeability and oral tolerance induction in mice. Furthermore, we observed that obese mice exhibited a more severe food allergy to OVA, and this allergy was alleviated after treatment with a hypoglycemic drug. Importantly, our findings were translated to obese humans. Individuals with T2D had higher serum IgE levels and downregulated genes related to gut homeostasis. Taken together, our results suggest that obesity-induced hyperglycemia can lead to a failure in oral tolerance and to exacerbation of food allergy. These findings shed light on the mechanisms underlying the relationship among obesity, T2D, and gut mucosal immunity, which could inform the development of new therapeutic approaches.

Surgical Approaches to Optic Disc Pit Maculopathy: A Clinical Case Series.

The purpose of this study was to compare the clinical outcomes of 13 patients with optic disc pit maculopathy (ODP-M) - progressive visual loss, serous macular detachment, and/or intraretinal fluid - who underwent different surgical approaches. This was a retrospective study including a consecutive sample of 13 patients aged 13-74 years (mean 35.38 ± 19.66 years) diagnosed with ODP-M and submitted to vitreoretinal surgery between 2005 and 2021. All patients underwent pars plana vitrectomy, posterior hyaloid detachment, and gas tamponade. Endolaser photocoagulation was applied to the temporal margin of the optic disc in 8 cases; internal limiting membrane (ILM) peeling was performed in 9 cases; and ILM inverted flap technique in 5 cases. Stuffing of the pit with an ILM flap was performed in 3 cases. Mean best-corrected visual acuity improved from 20/200 (1.04 ± 0.56 LogMAR) to 20/50 (0.43 ± 0.54 LogMAR) within 4-36 months. Central retinal thickness decreased from 587.5 ± 158.01 µm to 253.9 ± 33.55 µm, and 7 out of 10 patients had complete resolution of intraretinal fluid. All patients had complete retinal reattachment; however, a few years after surgery, 4 patients had recurrence of serous retinal detachment. The only adjunctive technique associated with greater visual improvement was endolaser (p = 0.033) and not performing peeling of the ILM was also associated with better visual results (p = 0.013), independently of preoperative visual acuity or age at the time of surgery. None of the adjunctive procedures was a significant predictor of better anatomical outcomes. In conclusion, all of these approaches for the surgical management of ODP-M were safe and effective. In this study, vitrectomy with endolaser was a good option for management of ODP-M.

Ocular Sarcoidosis and Autoimmune Polyglandular Syndrome Type 2: A Case Report.

PURPOSE: to describe a clinical case of ocular sarcoidosis in a patient with Autoimmune Polyglandular Syndrome Type 2 (APS-2). METHODS: an 86-year-old female diagnosed with APS-2 was referred to our uveitis department with rapid visual loss in her left eye during a 3-month period. Her best-corrected visual acuity (BCVA) was counting fingers in her left eye (OS) and 20/40 in her right eye (OD). Slit-lamp biomicroscopy was unremarkable OD but revealed granulomatous keratic precipitates OS. Fundoscopy revealed bilateral optic disc oedema and +2 and 4+ vitritis (SUN classification) in her OD and OS, respectively. RESULTS: the patient underwent chest X-Ray which revealed bilateral hilar lymphadenopathy and fibrosis. On high-resolution computed tomography of the lungs, ground-glass opacities were visible, and a diagnosis of ocular sarcoidosis was presumed. After exclusion of infectious diseases, the patient was treated with methotrexate and oral corticosteroids and there was substantial improvement of the optic nerve oedema and vitritis. At the most recent visit, 2 years later, OS BCVA was 20/50. CONCLUSION: There may be an association between ocular sarcoidosis and APS or other autoimmune disorders.

Oral tolerance as antigen-specific immunotherapy.

Oral tolerance is a physiological phenomenon described more than a century ago as a suppressive immune response to antigens that gain access to the body by the oral route. It is a robust and long-lasting event with local and systemic effects in which the generation of mucosally induced regulatory T cells (iTreg) plays an essential role. The idea of using oral tolerance to inhibit autoimmune and allergic diseases by oral administration of target antigens was an important development that was successfully tested in 1980s. Since then, several studies have shown that feeding specific antigens can be used to prevent and control chronic inflammatory diseases in both animal models and clinically. Therefore, oral tolerance can be classified as an antigen-specific form of oral immunotherapy (OIT). In the light of novel findings on mechanisms, sites of induction and factors affecting oral tolerance, this review will focus on specific characteristics of oral tolerance induction and how they impact in its therapeutic application.

A watershed impacted by anthropogenic activities: Microbial community alterations and reservoir of antimicrobial resistance genes.

Water is the main resource for maintaining life. Anthropic activities influence the microbial epidemiological chain in watersheds, which can act as ways of disseminating microorganisms resistant to antimicrobial drugs, with impacts on human, animal, and environmental health. Here, we characterized aquatic microbial communities and their resistomes in samples collected along Rio das Ostras watershed during two seasons. Surface water samples were collected at eleven sites from the Jundiá, Iriry, and Rio das Ostras rivers in two seasons (dry and wet season). Microbial DNA was extracted, high-throughput sequenced and screened for antimicrobial resistance genetic (ARG) markers. The physicochemical characteristics and the microbiota data confirmed that Rio das Ostras watershed can be divided into three well defined portions: rural, urban, and marine. Rural areas were enriched by bacteria typically found in limnic environments and Patescibacteria phyla. The urban portion was characterized by sites with low pH and groups associated with iron oxidation. Some genera of clinical relevance were also identified, though in relatively low abundance. The marine site was enriched mainly by Cyanobacteria and bacteria that showed strong correlation with conductivity, salinity, and chloride. Twenty-six ARG markers were identified on the resistome, being found most frequently in the urban area, despite being present in rural sites. Among them were some related to classes of great clinical concern, such as genes coding for extended-spectrum beta-lactamase (blaCTX-M and blaTEM), resistance to carbapenems (blaKPC) and to methicillin by Staphylococcus aureus (mecA). These results broaden our understanding of the microbial community of a watershed impacted by anthropogenic actions. The large number of ARGs detected along the Rio das Ostras watershed contrasts with the small number of microorganisms of clinical relevance observed, suggesting that antimicrobial resistance has arisen from non-clinical environments and microbes. Our results corroborate that freshwater acts as a reservoir of antimicrobial resistance genes.

Advanced Maternal Age: Adverse Outcomes of Pregnancy, A Meta-Analysis.

INTRODUCTION: The risks of pregnancy in women of advanced maternal age are not consensual amongst studies. The aim of this metaanalysis  was to determine whether women of advanced maternal age (≥ 35 years old) had worse obstetrical and perinatal outcomes than non- advanced maternal age women (20 - 34 years old) in singleton, naturally-conceived pregnancies. MATERIAL AND METHODS: We searched PubMed/ MEDLINE, IndexRMP and the Cochrane Database of Systematic Reviews. Ten studies were included according to the following criteria: population of > 1000 nulliparous and/or multiparous women with singleton gestations who did not undergo any type of infertility treatment. Using Review Manager v. 5.3, two meta-analysis were performed: one comparing the outcomes of 20 - 34-year-old vs 35 - 40-year-old women, and another comparing the outcomes of 35 - 40-year-old women vs > 40-year-old women. RESULTS: Women aged 35 - 40 years old were more likely to have > 12 years of education than 20 - 34 years old and > 40 years old women. Advanced maternal age women (35 - 40 and > 40 years old) were more likely to be overweight and having gestational diabetes and gestational hypertension. They were also more likely to undergo induced labour and elective caesarean deliveries. Furthermore, they had worse perinatal outcomes such as preterm delivery, low birthweight babies, higher rates of Neonatal Intensive Care Unit admission and worse Apgar scores. Advanced maternal age women had higher rates of perinatal mortality and stillbirth. DISCUSSION: Most authors present similar results to our study. Although the majority of adverse outcomes can be explained through the physio-pathological changes regarding the female reproductive apparatus that come with aging and its inherent comorbidities, according to the existing literature advanced maternal age can be an independent risk factor per se. In older pregnant women without comorbidities such as gestational hypertension or diabetes there are still worse obstetric and perinatal outcomes, which indicate that advanced maternal age is an independent strong risk factor alone. CONCLUSION: Advanced maternal age women are at a higher risk of adverse obstetrical and perinatal outcomes. In both comparisons, worse outcomes were more prevalent in the older group, suggesting that poorer outcomes are more prevalent with increasing age.

Introdução: Não há consenso na literatura sobre os riscos da gravidez em mulheres com idade materna avançada. O objetivo desta meta-análise consistiu em determinar se as mulheres com idade materna avançada (≥ 35) tiveram piores desfechos obstétricos e perinatais, comparativamente com as mulheres não-idade materna avançada (20 - 34 anos), em gestações de feto único e por conceção natural. Material e Métodos: A pesquisa bibliográfica foi feita na PubMed/MEDLINE, IndexRMP e na Cochrane Database of Systematic Reviews. Foram incluídos dez estudos segundo os seguintes critérios: população-estudo > 1000 mulheres, nulíparas e/ou multíparas, com gestações de feto único sem recurso a tecnologias de reprodução medicamente assistida. Duas meta-análises foram feitas com o programa Review Manager v. 5.3: uma comparando os desfechos da gravidez do grupo 20 - 34 anos com o grupo 35 - 40 anos e outra comparando os grupos de idades 35 - 40 e > 40 anos. Resultados: As mulheres com 35 - 40 anos tiveram mais probabilidade de ter > 12 anos de escolaridade, comparativamente ao grupo 20 - 34 e > 40 anos. Mulheres com idade materna avançada (35 - 40 e > 40 anos) tiveram maior probabilidade de ter excesso de peso e comorbilidades como diabetes gestacional e hipertensão gestacional. Tiveram também maior frequência de partos induzidos e de cesarianas eletivas. As mulheres mais velhas tiveram mais partos pré-termo e recém-nascidos com baixo peso. Os bebés das mães com idade materna avançada foram mais vezes admitidos na Unidade de Cuidados Intensivos Neonatais e tiveram piores índices de Apgar. De igual forma, as mulheres com idade materna avançada tiveram maiores taxas de mortalidade perinatal e morte in utero. Discussão: A maioria dos autores descreve resultados semelhantes àqueles que estão descritos na meta-análise. Embora os resultados desfavoráveis sejam em grande parte explicados pela fisiopatologia do envelhecimento do sistema reprodutor da mulher e comorbilidades inerentes ao avançar da idade, a bibliografia admite a idade materna avançada um fator de risco per se. Mesmo em mulheres com idade materna avançada sem comorbilidades como diabetes ou hipertensão gestacional, esta acaba por ser um fator de risco independente e significativo para desfechos adversos. Conclusão: Mulheres com idade materna avançada têm um maior risco de desfechos obstétricos e perinatais adversos. Em ambas as comparações os piores desfechos foram mais prevalentes no grupo de mulheres com maior idade, sugerindo maior expressão com o avançar da idade.

Frontline Science: Abnormalities in the gut mucosa of non-obese diabetic mice precede the onset of type 1 diabetes.

Alterations in the composition of the intestinal microbiota have been associated with development of type 1 diabetes (T1D), but little is known about changes in intestinal homeostasis that contribute to disease pathogenesis. Here, we analyzed oral tolerance induction, components of the intestinal barrier, fecal microbiota, and immune cell phenotypes in non-obese diabetic (NOD) mice during disease progression compared to non-obese diabetes resistant (NOR) mice. NOD mice failed to develop oral tolerance and had defective protective/regulatory mechanisms in the intestinal mucosa, including decreased numbers of goblet cells, diminished mucus production, and lower levels of total and bacteria-bound secretory IgA, as well as an altered IEL profile. These disturbances correlated with bacteria translocation to the pancreatic lymph node possibly contributing to T1D onset. The composition of the fecal microbiota was altered in pre-diabetic NOD mice, and cross-fostering of NOD mice by NOR mothers corrected their defect in mucus production, indicating a role for NOD microbiota in gut barrier dysfunction. NOD mice had a reduction of CD103+ dendritic cells (DCs) in the MLNs, together with an increase of effector Th17 cells and ILC3, as well as a decrease of Th2 cells, ILC2, and Treg cells in the small intestine. Importantly, most of these gut alterations precede the onset of insulitis. Disorders in the intestinal mucosa of NOD mice can potentially interfere with the development of T1D due the close relationship between the gut and the pancreas. Understanding these early alterations is important for the design of novel therapeutic strategies for T1D prevention.

Identification and characterization of latency-associated peptide-expressing γδ T cells.

γδ T cells are a subset of lymphocytes specialized in protecting the host against pathogens and tumours. Here we describe a subset of regulatory γδ T cells that express the latency-associated peptide (LAP), a membrane-bound TGF-ß1. Thymic CD27+IFN-γ+CCR9+α4ß7+TCRγδ+ cells migrate to the periphery, particularly to Peyer's patches and small intestine lamina propria, where they upregulate LAP, downregulate IFN-γ via ATF-3 expression and acquire a regulatory phenotype. TCRγδ+LAP+ cells express antigen presentation molecules and function as antigen presenting cells that induce CD4+Foxp3+ regulatory T cells, although TCRγδ+LAP+ cells do not themselves express Foxp3. Identification of TCRγδ+LAP+ regulatory cells provides an avenue for understanding immune regulation and biologic processes linked to intestinal function and disease.

Vitamin A supplementation leads to increases in regulatory CD4+Foxp3+LAP+ T cells in mice.

Dietary compounds, including micronutrients such as vitamin A and its metabolite retinoic acid, directly influence the development and function of the immune system. In this study, we show that either dietary deficiency of or supplementation with vitamin A had immunologic effects in mice that were fed these diets during their development (for 8 wk during the postweaning period). Deficient mice presented higher levels of interferon-γ, interleukin (IL)-6, transforming growth factor-ß, IL-17, and IL-10 in the gut-associated lymphoid tissues and draining lymph nodes, indicating a proinflammatory shift in the gut mucosa. Serum immunoglobulin G levels also were elevated in these mice. Conversely, supplemented mice showed higher frequencies of CD4+Foxp3+LAP+ regulatory T cells in gut lymphoid tissues and spleen, suggesting that vitamin A supplementation in the diet may be beneficial in pathologic situations such as inflammatory bowel diseases.