Development Of Lymphoid Tissue Research Articles

Spleen Morphogenesis during the Neonatal Period in Rats Exposed to Endocrine Disruptor DDT

Spleen morphogenesis during the neonatal period in rats exposed in prenatal and postnatal development to low doses of dichlorodiphenyltrichloroethane (DDT), a persistent universal pollutant with endocrine disrupting properties, was studied. More intensive formation of periarterial lymphoid sheaths and marginal zone and simultaneously decreased rate of B-cell differentiation in the spleen were revealed. A higher content of differentiating T-cells and a lower number of cytotoxic T-lymphocytes by the end of the first week of life indicates a decrease in the differentiation of the latter. A lower content of neutrophils in the marginal zone also indicates a delay in the rate of functional development of lymphoid tissue, as opposed to morphological, in rats developing under exposure to low doses of DDT.

The bidirectional interplay of obstructive sleep apnea and viral respiratory infections in children: A novel opportunity for primary prevention.

Obstructive sleep apnea (OSA) and viral respiratory infections are highly prevalent conditions in children and a major cause of respiratory morbidity in this age group. Severe viral respiratory infections are a known risk factor for pediatric OSA, which is primarily caused by hypertrophy of upper airway lymphoid tissues (adenoids and tonsils). This review examines recent progress in understanding early-life development of lymphoid tissues in the human upper airway, with a particular focus on how respiratory viruses may influence this process and contribute to OSA pathogenesis. It also explores the bidirectional relationship between OSA and severe viral infections, highlighting the need for ongoing monitoring and novel primary prevention strategies to address these interconnected conditions.

MicroRNA-142 regulates gut associated lymphoid tissues and group 3 innate lymphoid cells

The transcriptomic signatures that shape responses of innate lymphoid cells (ILCs) have been well characterised, however post-transcriptional mechanisms which regulate their development and activity remain poorly understood. We demonstrate that ILC groups of the intestinal lamina propria express mature forms of microRNA-142 (miR-142), an evolutionarily conserved microRNA family with several non-redundant regulatory roles within the immune system. Germline Mir142 deletion alters intestinal ILC compositions, resulting in the absence of T-bet+ populations and significant defects in the cellularity and phenotypes of ILC3 subsets including CCR6+ LTi-like ILC3s. These effects were associated with decreased pathology in an innate-immune cell driven model of colitis. Furthermore, Mir142−/− mice demonstrate defective development of gut-associated lymphoid tissues, including a complete absence of mature Peyer’s patches. Conditional deletion of Mir142 in ILC3s (RorcΔMir142) supported cell-intrinsic roles for these microRNAs in establishing or maintaining cellularity and functions of LTi-like ILC3s in intestinal associated tissues. RNAseq analysis revealed several target genes and biological pathways potentially regulated by miR-142 microRNAs in these cells. Finally, lack of Mir142 in ILC3 led to elevated IL-17A production. These data broaden our understanding of immune system roles of miR-142 microRNAs, identifying these molecules as critical post-transcriptional regulators of ILC3s and intestinal mucosal immunity.

The Microbiota in Cancer: A Secondary Player or a Protagonist?

The intestinal microbiota and the human body are in a permanent interaction. There is a symbiotic relationship in which the microbiota plays a vitally important role in the performance of numerous functions, including digestion, metabolism, the development of lymphoid tissue, defensive functions, and other processes. It is a true metabolic organ essential for life and has potential involvement in various pathological states, including cancer and pathologies other than those of a digestive nature. A growing topic of great interest for its implications is the relationship between the microbiota and cancer. Dysbiosis plays a role in oncogenesis, tumor progression, and even the response to cancer treatment. The effect of the microbiota on tumor development goes beyond a local effect having a systemic effect. Another aspect of great interest regarding the intestinal microbiota is its relationship with drugs, modifying their activity. There is increasing evidence that the microbiota influences the therapeutic activity and side effects of antineoplastic drugs and also modulates the response of several tumors to antineoplastic therapy through immunological circuits. These data suggest the manipulation of the microbiota as a possible adjuvant to improve oncological treatment. Is it possible to manipulate the microbiota for therapeutic purposes?

Aryl hydrocarbon receptor activity in intestinal epithelial cells in the formation of colonic tertiary lymphoid tissues.

After birth, the development of secondary lymphoid tissues (SLTs) in the colon is dependent on the expression of the aryl hydrocarbon receptor (AhR) in immune cells as a response to the availability of AhR ligands. However, little is known about how AhR activity from intestinal epithelial cells (IECs) may influence the development of tertiary lymphoid tissues (TLTs). As organized structures that develop at sites of inflammation or infection during adulthood, TLTs serve as localized centers of adaptive immune responses, and their presence has been associated with the resolution of inflammation and tumorigenesis in the colon. Here, we investigated the effect of the conditional loss of AhR activity in IECs in the formation and immune cell composition of TLTs in a model of acute inflammation. In females, loss of AhR activity in IECs reduced the formation of TLTs without significantly changing disease outcomes or immune cell composition within TLTs. In males lacking AhR expression in IECs, increased disease activity index, lower expression of functional-IEC genes, increased number of TLTs, increased T-cell density, and lower B- to T-cell ratio were observed. These findings may represent an unfavorable prognosis when exposed to dextran sodium sulfate (DSS)-induced epithelial damage compared with females. Sex and loss of IEC AhR also resulted in changes in microbial populations in the gut. Collectively, these data suggest that the formation of TLTs in the colon is influenced by sex and AhR expression in IECs.NEW & NOTEWORTHY This is the first research of its kind to demonstrate a clear connection between biological sex and the development of tertiary lymphoid tissues (TLT) in the colon. In addition, the research finds that in a preclinical model of inflammatory bowel disease, the expression of the aryl hydrocarbon receptor (AhR) influences the development of these structures in a sex-specific manner.

Developmental Exposure To Low Doses Of Dichlorodiphenyltrichloroethane Disrupts Functional And Morphologic Maturation Of The Spleen In Prepubertal Rats

Dichlorodiphenyltrichloroethane (DDT) is a versatile persistent pollutant with endocrine disrupting properties and an alleged immune modulator. Objective — to evaluate the parameters of functional and morphological maturation of the spleen in prepubertal rats exposed to low doses of DDT. Material and Methods — From the moment of mating, during pregnancy and lactation, female rats received a solution of o,p-DDT (20 μg/L) instead of tap water. The offspring of intact rat dams were considered the control group. Male DDT-exposed and control rats were sacrificed on postnatal day 7. The spleens were surgically removed under sterile conditions. Anatomical and histological examination of the spleen, ex tempore proliferation of splenocytes, and assessment of splenic T cells and their ability to respond to the mitogen concanavalin A were assessed. Results — Rats exposed to DDT exhibited a significantly reduced proliferative response of spleen lymphocytes to the mitogen concanavalin A. However, morphological evaluation revealed no differences in spleen anatomy between control and exposed rats. Histological examination exposed accelerated development of lymphoid tissue in the spleen of rats exposed to DDT. The ex-tempore proliferation test yielded a higher rate of mitotic division of splenocytes in exposed rats. In contrast to controls, they had a lower percentage of T cells in their spleen. Conclusion — Developmental exposure to low doses of the endocrine disruptor DDT impairs functional and morphological maturation of the spleen in prepubertal rats. DDT accelerates the formation of lymphoid compartments and weakens the functional maturation of the spleen as the organ with an immune function.

Impact of early posthatch feeding on the immune system and selected hematological, biochemical, and hormonal parameters in broiler chickens

Under commercial conditions, chicks hatch within a 24 to 48 h window, a period known as the hatching window. Subsequently, they undergo various treatments before finally being transported to the broiler farm. These procedures may delay the chicks' access to food and water, sometimes receiving them as late as 72 h after hatching. Previous studies have indicated that fasting during this initial period is detrimental, leading to impaired body growth, compromised immune system response, and hindered muscle development. The objective of this study was to assess the impact of early posthatch feeding on immune system organs and selected hematological, biochemical, and hormonal parameters. The experiment utilized Ross 308 broiler eggs incubated under typical commercial hatchery conditions. The experimental group's eggs were hatched in HatchCare hatchers (HC) with immediate access to feed and water, while the control group's eggs were hatched under standard conditions (ST). Thirty chickens from each group were assessed on the 1st (D1), 7th (D7), 21st (D21), and 35th (D35) day after hatching. On D1, the HC group exhibited lower hemoglobin, hematocrit, and total serum protein values, suggesting that early access to water prevents initial dehydration in newborn chicks. Conversely, the ST group showed a stress reaction on D1 due to feed deprivation, leading to an almost 2-fold higher serum corticosterone concentration compared to the HC group. However, this increase did not result in a significant change in the heterophil/lymphocyte ratio. Furthermore, the HC group displayed an increase in triglyceride concentration and a decrease in HDL concentration on D1. On D7, the HC group exhibited an increased relative weight of the bursa and a higher CD4+ cell number in the cecal tonsil (CT), indicating a more rapid development of these organs resulting from early stimulation of the gastrointestinal tract. However, early feeding did not influence the numbers of Bu-1+, CD4+, and CD8+ cells or the germinal center (GC) areas in the spleen. In conclusion, early feeding contributes to the welfare of newborn chicks by reducing dehydration and stress levels and stimulating the development of gut-associated lymphoid tissue.

Distribution and spatiotemporal development of organised lymphoid tissues in the chicken intestinal tract

Chickens exhibit a distinct immune architecture characterised by the absence of draining lymph nodes and the presence of a well-developed mucosa-associated lymphoid tissue. The structure and spatiotemporal development of chicken lymphoid tissues in the intestine are poorly documented. The macroscopically indistinct structure of chicken Peyer's patches has impeded studies into their development. The generation of CSF1R-eGFP reporter transgenic chickens enables visualisation of the development, organisation and extent of chicken lymphoid tissues by unique macroscopic views. CSF1R-eGFP reporter transgenic chickens were used to investigate the distribution and spatiotemporal development of PP and caecal tonsils in embryonic day 18 to 8-week-old chickens. Peyer's patch anlagen are present at ED18 with a similar frequency and distribution pattern observed in 2- and 8-week-old chickens. These findings can support in ovo and post-hatch mucosal vaccination strategies and the development of vaccine delivery systems targeted to the specialized epithelium overlying the Peyer's patches.

Single-Nucleus RNA Sequencing Reveals Cellular Heterogeneity and Cell-Cell Interactions Contributing to Tertiary Lymphoid Tissue Development in the Aged Injured Kidney

Single-Nucleus RNA Sequencing Reveals Cellular Heterogeneity and Cell-Cell Interactions Contributing to Tertiary Lymphoid Tissue Development in the Aged Injured Kidney

Abstract 3443: Aryl hydrocarbon receptor and its ligands influence the formation of colonic tertiary lymphoid tissues

Abstract Background: In the large intestine, tertiary lymphoid tissues (TLTs) serve as localized centers of adaptive immune responses. These structures often form in response to inflammation and infection during adulthood. However, more recently TLTs have become a focal point of colon caner development and progression as their presence is often associated with positive clinical outcomes. Interestingly, several studies have demonstrated that the aryl hydrocarbon receptor (AhR) influences the development of secondary lymphoid tissues, but minimal studies have focused on its role in TLT formation. The purpose of the presented studies was to test the hypothesis that activation of AhR in intestinal epithelial cells (IECs) induces the formation of TLTs in the colon. Methods: Wild type (WT) and IEC-specific AhR knockout (CDX2PCreT2 x AhRf/f- iAhRKO) mice were used in several different experimental models. In the first study, azoxymethane (AOM) was used to induce precancerous lesions in the colon and TLT formation was evaluated in the presence and absence of AhR. Then, experiments were conducted to determine the necessity of AhR expression in IECs to influence the formation of TLTs following induction of acute inflammation induced by Dextran sodium sulfate (DSS) exposure. Finally, the ability of known, naturally occurring and microbial-derived AhR ligands (indole-3-aldehyde (I3A), 3,3ʹ-diindolylmethane (DIM), and indole-3-acetic acid (IAA)) were tested for their ability to induce TLT formation in the colon. Intestinal permeability (FITC-Dextran), expression of IEC-associated genes (real-time qPCR), and TLT formation/composition (H&E staining/Immunofluorescence) were evaluated. Results: Results from the first study demonstrated that IEC-specific AhR KO mice exposed to AOM developed significantly fewer TLTs when compared to WT controls, while expression of Il-22 and other chemokines involved in TLT formation were also significantly downregulated. In the acute inflammation study, sex specific results were found. In females, loss of AhR activity in IECs reduced the formation of TLTs without significant changes in immune cell composition within their TLTs. Conversely, in males, loss of AhR lowered expression of functional-IEC genes (Ocln, Il-22), increased number of TLTs, increased T-cell density, and lower B: T cell ratio. Finally, in the other experiments, I3A induced TLT formation and DIM promoted intestinal barrier integrity through the upregulation of various tight junction genes and genes involved in the signaling associated with TLT formation. Evaluation of IAA which is a microbial-derived, AhR ligand is ongoing. Conclusion: These data indicate that AhR plays a distinct role in the formation of TLTs in the colon and these effects are likely ligand specific and may have a significant effect on colon tumor formation. Citation Format: Kimberly F. Allred, Erika L. Garcia-Villatoro, Jennifer DeLuca, Victoria Tepe, Zachary Bomstein, Arinzechukwu Ufondu, Stephen H. Safe, Robert S. Chapkin, Arul Jayaraman, Clinton D. Allred. Aryl hydrocarbon receptor and its ligands influence the formation of colonic tertiary lymphoid tissues [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3443.

Controversial role of ILC3s in intestinal diseases: A novelty perspective on immunotherapy.

ILC3s have been identified as crucial immune regulators that play a role in maintaining host homeostasis and modulating the antitumor response. Emerging evidence supports the idea that LTi cells play an important role in initiating lymphoid tissue development, while other ILC3s can promote host defense and orchestrate adaptive immunity, mainly through the secretion of specific cytokines and crosstalk with other immune cells or tissues. Additionally, dysregulation of ILC3-mediated overexpression of cytokines, changes in subset abundance, and conversion toward other ILC subsets are closely linked with the occurrence of tumors and inflammatory diseases. Regulation of ILC3 cytokines, ILC conversion and LTi-induced TLSs may be a novel strategy for treating tumors and intestinal or extraintestinal inflammatory diseases. Herein, we discuss the development of ILCs, the biology of ILC3s, ILC plasticity, the correlation of ILC3s and adaptive immunity, crosstalk with the intestinal microenvironment, controversial roles of ILC3s in intestinal diseases and potential applications for treatment.

The Lipid-Soluble Forms of Choline Enhance Ex Vivo Responses from the Gut-Associated Immune System in Young Female Rat Offspring

In humans, the development of gut-associated lymphoid tissue (GALT) occurs in the first years of life and can be influenced by diet. The objective of this study was to determine the effect of dietary choline on the development of gut-associated lymphoid tissue (GALT). Three feeding trials were conducted in female Sprague-Dawley rats. Beginning 3 d before parturition (studies 1 and 3) or at day 10 of gestation (study 2), control dams consumed a 100% free choline (FC) diet until the end of the lactation period. In studies 1 and 3, test dams consumed a high-glycerophosphocholine (HGPC) diet [75% glycerophosphocholine (GPC), 12.5% phosphatidylcholine (PC), 12.5% FC] and a 100% PC diet, respectively (both 1 g of choline/kg diet). In study 2, test dams consumed a high-sphingomyelin (SM) and PC (SMPC) diet (34% SM, 37% PC, 17% GPC, 7% FC, 5% phosphocholine) or a 50% PC diet (50% PC, 25% FC, 25% GPC), both 1.7 g of choline/kg diet. Immune cell phenotypes and ex vivo cytokine production by mitogen-stimulated immune cells were measured. Feeding of the HGPC diet lowered T-cell IL-2 (44%), IFN-γ (34%), and TNF-α (55%) production in mesenteric lymph nodes (MLNs) compared with control. Feeding both SMPC and 50% PC diets during the lactation and weaning periods increased IL-2 (54%) and TNF-α (46%) production after T-cell stimulation compared with control. There was a lower production of IL-2 (46%), IL-6 (66%), and TNF-α (45%), and a higher production of IL-10 (44%) in both SMPC and 50% PC groups following ovalbumin stimulation compared with control in MLNs. Feeding a diet containing 100% PC increased the production of IFN-γ by 52% after T-cell stimulation compared with control. Feeding a diet containing a mixture of choline forms with a high content of lipid-soluble forms during both the lactation and weaning periods enhances ex vivo immune responses from the GALT in female Sprague-Dawley offspring.

Biliary NIK promotes ductular reaction and liver injury and fibrosis in mice

Excessive cholangiocyte expansion (ductular reaction) promotes liver disease progression, but the underlying mechanism is poorly understood. Here we identify biliary NF-κB-inducing kinase (NIK) as a pivotal regulator of ductular reaction. NIK is known to activate the noncanonical IKKα/NF-κB2 pathway and regulate lymphoid tissue development. We find that cholangiocyte NIK is upregulated in mice with cholestasis induced by bile duct ligation (BDL), 5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), or α-naphtyl-isothiocyanate (ANIT). DDC, ANIT, or BDL induces ductular reaction, liver injury, inflammation, and fibrosis in mice. Cholangiocyte-specific deletion of NIK, but not IKKα, blunts these pathological alterations. NIK inhibitor treatment similarly ameliorates DDC-induced ductular reaction, liver injury, and fibrosis. Biliary NIK directly increases cholangiocyte proliferation while suppressing cholangiocyte death, and it also promotes secretion of cholangiokines from cholangiocytes. Cholangiokines stimulate liver macrophages and hepatic stellate cells, augmenting liver inflammation and fibrosis. These results unveil a NIK/ductular reaction axis and a NIK/cholangiokine axis that promote liver disease progression.

Relationship between intestinal hyperpermeability and obesity

Obesity is a combination of genetic, environmental factors, and systemic inflammation of adipose tissue. In the last decade, more and more evidence suggests that intestinal microbiota is an environmental factor that plays a crucial role in obesity and associated metabolic disorders. Here, we review the association between intestinal microbiota and obesity based on the literature data available to us. The intestinal flora, in the equilibrium state of conventional bacteria, protects the health of the host and helps the development of the immune system. The genome, diet, lifestyle, and epigenetic changes of the host can pathologically alter the composition of the microbiota. In dysbiosis, the development of the gut-associated lymphoid tissue (GALT) associated with the intestinal tract is impaired and the integrity of the intestinal barrier is impaired. Due to the consequent intestinal hyperpermeability, components of pathogenic pathogens such as lipopolysaccharides enter the bloodstream. These components bind to receptors on adipose tissue immune cells as ligands for molecular samples with pathogenic properties and induce adipose tissue dysfunction. The secretion of inflammatory cytokines in adipose tissue is increased. This induces persistent low chronic inflammation, which is responsible for the development of obesity. The damage to health caused by the hyperpermeability of the intestinal barrier can be reduced by interventions, or restored early in the process. Knowing the relationships will help prevent and treat obesity.

LTβR overexpression promotes plasma cell accumulation.

Multiple myeloma (MM), a malignancy of plasma cells (PCs), has diverse genetic underpinnings and in rare cases these include amplification of the lymphotoxin b receptor (Ltbr) locus. LTβR has well defined roles in supporting lymphoid tissue development and function through actions in stromal and myeloid cells, but whether it is functional in PCs is unknown. Here we showed that Ltbr mRNA was upregulated in mouse PCs compared to follicular B cells, but deficiency in the receptor did not cause a reduction in PC responses to a T-dependent or T-independent immunogen. However, LTβR overexpression (OE) enhanced PC formation in vitro after LPS or anti-CD40 stimulation. In vivo, LTβR OE led to increased antigen-specific splenic and bone marrow (BM) plasma cells responses. LTβR OE PCs had increased expression of Nfkb2 and of the NF-kB target genes Bcl2 and Mcl1, factors involved in the formation of long-lived BM PCs. Our findings suggest a pathway by which Ltbr gene amplifications may contribute to MM development through increased NF-kB activity and induction of an anti-apoptotic transcriptional program.

Macro-microscopic features of the structure of lymphoid nodules in the wall of the female urethra

The aim of the investigation was to study the macro-microscopic features of the structure and quantitative indicators of the lymphoid nodules of the female urethra in postnatal ontogenesis.Material and methods. The topography, number and size of lymphoid nodules in the urethral wall from corpses of 63 women of different age groups were studied by macro-microscopy using binocular stereomicroscope MBS-9 after elective staining with Harris hematoxylin. The material was fixed in a 10% formalin solution. The preparations were photographed and the area of lymphoid nodules was measured in the ImageJ program. For statistical data processing, parametric statistics methods based on the Statistica 6.0 program were used. Statistical data processing included the calculation of arithmetic averages, their errors, and the analysis of the amplitude of the variation series of each indicator.Results. The maximum number of lymphoid nodules in the urethra in early childhood corresponds to the idea of the largest total number of lymphoid cells, the severity of lymphoid tissue in the first years of life. The density of lymphoid nodules is maximum in the 1st period of childhood (9,5–10,5 nodules), and then decreases sequentially. In senile age, compared with the 1st period of childhood, the density of localization of lymphoid nodules decreases in the walls of the upper third of the urethra by 1.7 times (p< 0.05), the middle and lower thirds of the organ - by 1.2 times (p<0.05) and the urethra as a whole – by 1.3 times (p<0.05). The amplitude of the variation series (differences between individual maximum and minimum) of the density of the location of lymphoid nodules, according to our data, does not change significantly during postnatal ontogenesis. The size of the lymphoid nodule during postnatal ontogenesis is maximal in the 1st period of childhood. Further, the value of this indicator decreases and reaches a minimum in old age and in centenarians.Conclusion. The study showed that lymphoid tissue in the urethral wall is at different stages of morphogenetic maturity, lymphoid nodules are found, which, as is known, are considered to be a more functionally mature stage of lymphoid tissue development. The values of the density of the location of lymphoid nodules throughout the female urethra in postnatal ontogenesis change slightly, the minimum number of them is observed in old age and the period of longevity, the maximum does not actually change.

Do Intestinal Microbiota and Thyroid Travel in Tandem?

The gut microbiota exerts some pivotal metabolic functions in digestion and absorption of nutrients [1], detoxification and synthesis of vitamins [2]. Furthermore, it is essential in correct development of lymphoid tissue associated with intestine (GALT) [3], the largest component of the lymphoid system, which contains over 70% of the total immune system.

The Efficacy of Cancer Immunotherapies Is Compromised by Helicobacter pylori Infection.

Helicobacter pylori infects the gastric mucosa of a large number of humans. Although asymptomatic in the vast majority of cases, H pylori infection can lead to the development of peptic ulcers gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. Using a variety of mechanisms, H pylori locally suppresses the function of the host immune system to establish chronic infection. Systemic immunomodulation has been observed in both clinical and pre-clinical studies, which have demonstrated that H pylori infection is associated with reduced incidence of inflammatory diseases, such as asthma and Crohn’s disease. The introduction of immunotherapies in the arsenal of anti-cancer drugs has revealed a new facet of H pylori-induced immune suppression. In this review, we will describe the intimate interactions between H pylori and its host, and formulate hypothtyeses describing the detrimental impact of H pylori infection on the efficacy of cancer immunotherapies.

Early Life Development of Bronchial Associated Lymphoid Tissue Containing Germinal Center in the Human Lung

Abstract Early life susceptibility to respiratory pathogens is well established in infants and young children, however the specific adaptations of the infant immune system for responding to multiple respiratory challenges are not known. Here, we examined lung and lung-associated lymph nodes derived from infant and pediatric organ donors (0–13 years) by confocal immunofluorescence and high dimensional flow cytometry. We identified early formation of bronchial associated lymphoid tissue (BALT) where active immune responses are initiated. At 8 days of life, few immune cells were present around the airways. By 5 months old, we start to observe BALT formation. However, BALT lose their structure with aging and are mostly absent by 10 years of age with CD4 memory T cells dominating the population around the central airways. Germinal centers are seen in 50–60% of BALT during the first two years of life. The percentage of BALT with germinal centers decreases over age, while germinal center formation in lung lymph nodes is maintained throughout infancy and childhood. Flow cytometry data shows seeding of transitional and immature B cells in the lung during infancy, which decreases over age. However, proportion of IgG and IgA memory B cells increases significantly over age both in the lung and lung lymph nodes. The frequency of naïve B cells is stable throughout childhood in both sites. Our results suggest that localized tertiary lymphoid structures in pediatric lungs may be an important mechanism for mobilizing rapid in situ protection during the first few years of life when memory T cells and B cells are not fully established. Supported by grants listed below: “Human Atlas of Neonatal Development and Early Life-Immunity (HANDEL-I)”(award Number 2018PG-T1D071 The Leona M. and Harry B. Helmsley Charitable Trust) “Immunobiology and alveolar physiology of the aging lung” (U01 HL145547, NIH/NHLBI )

The impact of the gut microbiota on T cell ontogeny in the thymus.

The intestinal microbiota is critical for the development of gut-associated lymphoid tissues, including Peyer's patches and mesenteric lymph nodes, and is instrumental in educating the local as well as systemic immune system. In addition, it also impacts the development and function of peripheral organs, such as liver, lung, and the brain, in health and disease. However, whether and how the intestinal microbiota has an impact on T cell ontogeny in the hymus remains largely unclear. Recently, the impact of molecules and metabolites derived from the intestinal microbiota on T cell ontogeny in the thymus has been investigated in more detail. In this review, we will discuss the recent findings in the emerging field of the gut-thymus axis and we will highlight the current questions and challenges in the field.