Line Of Defense Research Articles

Biological variability of human intraepithelial lymphocytes throughout the human gastrointestinal tract in health and coeliac disease.

Intraepithelial lymphocytes are the first line of defence of the human intestinal immune system. Besides, their composition is altered on patients with coeliac disease (CD), so they are considered as biomarkers with utility on their diagnose and/or monitoring. Our aim is to address their variability through the human gastrointestinal tract in health and characterized them in further depth in the coeliac duodenum. Intraepithelial lymphocytes were isolated from human gastric, duodenal, ileal and colonic biopsies, then stained with specific antibodies and acquired by flow cytometry. Our results confirmed that the profile of Intraepithelial lymphocytes change through the length of the human gastrointestinal tract. Besides and given the central role that Interleukin-15 (IL-15) elicits on CD pathogenesis; we also assessed the expression of its receptor revealing that there was virtually no functional IL-15 receptor on duodenal Intraepithelial lymphocytes. Nevertheless and contrary to our expectations, the active IL-15 receptor was not increased either on Intraepithelial lymphocytes from CD patients. IL-15 might require additional stimulus to activate intraepithelial lymphocytes. These findings may provide novel tools to aid on a CD diagnosis and/or monitoring, at the time that provide the bases to perform functional studies in order of getting a deeper insight in the specific function that Intraepithelial lymphocytes elicit on CD pathogenesis.

Genome-Wide Association Study of Cuticle and Lipid Droplet Properties of Cucumber (Cucumis sativus L.) Fruit.

The fruit surface is a critical first line of defense against environmental stress. Overlaying the fruit epidermis is the cuticle, comprising a matrix of cutin monomers and waxes that provides protection and mechanical support throughout development. The epidermal layer of the cucumber (Cucumis sativus L.) fruit also contains prominent lipid droplets, which have recently been recognized as dynamic organelles involved in lipid storage and metabolism, stress response, and the accumulation of specialized metabolites. Our objective was to genetically characterize natural variations for traits associated with the cuticle and lipid droplets in cucumber fruit. Phenotypic characterization and genome-wide association studies (GWAS) were performed using a resequenced cucumber core collection accounting for >96% of the allelic diversity present in the U.S. National Plant Germplasm System collection. The collection was grown in the field, and fruit were harvested at 16-20 days post-anthesis, an age when the cuticle thickness and the number and size of lipid droplets have stabilized. Fresh fruit tissue sections were prepared to measure cuticle thickness and lipid droplet size and number. The collection showed extensive variation for the measured traits. GWAS identified several QTLs corresponding with genes previously implicated in cuticle or lipid biosynthesis, including the transcription factor SHINE1/WIN1, as well as suggesting new candidate genes, including a potential lipid-transfer domain containing protein found in association with isolated lipid droplets.

CRISPR-Mediated Viral Gene Knockout to Investigate Viral Evasion of Antiviral Innate Immunity.

The innate immune system relies on a variety of pathogen recognition receptors (PRRs) as the first line of defense against pathogenic invasions. Viruses have evolved multiple strategies to evade the host immune system through coevolution with hosts. The CRISPR-Cas system is an adaptive immune system in bacteria or archaea that defends against viral reinvasion by targeting nucleic acids for cleavage. Based on the characteristics of Cas proteins and their variants, the CRISPR-Cas system has been developed into a versatile gene-editing tool capable of gene knockout or knock-in operations to achieve genetic variations in organisms. It is now widely used in the study of viral immune evasion mechanisms. This chapter will introduce the use of the CRISPR-Cas9 system for editing herpes simplex virus 1 (HSV-1) genes to explore the mechanisms by which HSV-1 evades host innate immunity and the experimental procedures involved.

A Guideline Strategy for Identifying a Viral Gene/Protein Evading Antiviral Innate Immunity.

Antiviral innate immunity is the first line of defence against viruses. The interferon (IFN) signaling pathway, the DNA damage response (DDR), apoptosis, endoplasmic reticulum (ER) stress, and autophagy are involved in antiviral innate immunity. Viruses abrogate the antiviral immune response of cells to replication in various ways. Viral genes/proteins play a key role in evading antiviral innate immunity. Here, we will discuss the interference of viruses with antiviral innate immunity and the strategy for identifying viral gene/protein immune evasion.

In Vitro and In Vivo Evaluation of Virus-Induced Innate Immunity in Mouse.

The innate immune system is the first line of host defense against infection by pathogenic microorganisms, among which macrophages are important innate immune cells. Macrophages are widely distributed throughout the body and recognize and eliminate viruses through pattern recognition receptors (PRRs) to sense pathogen-associated molecular patterns (PAMPs). In the present chapter, we provide detailed protocols for vesicular stomatitis virus (VSV) amplification, VSV titer detection, isolation of mouse primary peritoneal macrophages, in vitro and in vivo VSV infection, detection of interferon-beta (IFN-β) expression, and lung injury. These protocols provide efficient and typical methods to evaluate virus-induced innate immunity in vitro and in vivo.

Rhinovirus infection of airway epithelial cells uncovers the non-ciliated subset as a likely driver of genetic risk to childhood-onset asthma

Asthma is a complex disease caused by genetic and environmental factors. Studies show that wheezing during rhinovirus infection correlates with childhood asthma development. Over 150 non-coding risk variants for asthma have been identified, many affecting gene regulation in Tcells, but the effects of most risk variants remain unknown. We hypothesized that airway epithelial cells could also mediate genetic susceptibility to asthma given they are the first line of defense against respiratory viruses and allergens. We integrated genetic data with transcriptomics of airway epithelial cells subject to different stimuli. We demonstrate that rhinovirus infection significantly upregulates childhood-onset asthma-associated genes, particularly in non-ciliated cells. This enrichment is also observed with influenza infection but not with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or cytokine activation. Overall, our results suggest that rhinovirus infection is an environmental factor that interacts with genetic risk factors through non-ciliated airway epithelial cells to drive childhood-onset asthma.

Changes in monocyte subsets in volunteers who received an oral wild-type Salmonella Typhi challenge and reached typhoid diagnosis criteria.

An oral Controlled Human Infection Model (CHIM) with wild-type S. Typhi was re-established allowing us to explore the development of immunity. In this model, ~55% of volunteers who received the challenge reached typhoid diagnosis criteria (TD), while ~45% did not (NoTD). Intestinal macrophages are one of the first lines of defense against enteric pathogens. Most organs have self-renewing macrophages derived from tissue-resident progenitor cells seeded during the embryonic stage; however, the gut lacks these progenitors, and all intestinal macrophages are derived from circulating monocytes. After infecting gut-associated lymphoid tissues underlying microfold (M) cells, S. Typhi causes a primary bacteremia seeding organs of the reticuloendothelial system. Following days of incubation, a second bacteremia and clinical disease ensue. S. Typhi likely interacts with circulating monocytes or their progenitors in the bone marrow. We assessed changes in circulating monocytes after CHIM. The timepoints studied included 0 hours (pre-challenge) and days 1, 2, 4, 7, 9, 14, 21 and 28 after challenge. TD participants provided extra samples at the time of typhoid diagnosis, and 48-96 hours later (referred as ToD). We report changes in Classical Monocytes -CM-, Intermediate Monocytes -IM- and Non-classical Monocytes -NCM-. Changes in monocyte activation markers were identified only in TD participants and during ToD. CM and IM upregulated molecules related to interaction with bacterial antigens (TLR4, TLR5, CD36 and CD206). Of importance, CM and IM showed enhanced binding of S. Typhi. Upregulation of inflammatory molecules like TNF-α were detected, but mechanisms involved in limiting inflammation were also activated (CD163 and CD354 downregulation). CM upregulated molecules to interact/modulate cells of the adaptive immunity, including T cells (HLA-DR, CD274 and CD86) and B cells (CD257). Both CM and IM showed potential to migrate to the gut as integrin α4β7 was upregulated. Unsupervised analysis revealed 7 dynamic cell clusters. Five of these belonged to CM showing that this is the main population activated during ToD. Overall, we provide new insights into the changes that diverse circulating monocyte subsets undergo after typhoid diagnosis, which might be important to control this disease since these cells will ultimately become intestinal macrophages once they reach the gut.

Heat shock protein (Hsp27)-ceramide synthase (Cers1) protein-protein interactions provide a new avenue for unexplored anti-cancer mechanism and therapy

Hsp27 is a member of the small heat-shock proteins (sHSPs) – the known cellular line of defence against abnormal protein folding behaviors. Nevertheless, its upregulation is linked to a variety of pathological disorders, including several types of cancers. The ceramide synthases (CerS) mediate the synthesis of ceramide, a critical structural and signaling lipid. Functionally, downstream ceramide metabolites are implicated in the apoptosis process and their abnormal functionality has been linked to anticancer resistance. Studies showed that CerS1 are possibly inhibited by Hsp27 leading to biochemical anticancer effects in vitro. Nevertheless, the nature of such protein-protein interaction (PPI) has not been considerably investigated in molecular terms, hence, we present the first description of the dynamics CerS1-Hsp27 interaction landscapes using molecular dynamics simulations. Time-scale molecular dynamics simulation analysis indicated a system-wide conformational events of decreased stability, increased flexibility, reduced compactness, and decreased folding of CerS1. Analysis of binding energy showed a favorable interaction entailing 56 residues at the interface and a total stabilizing energy of −158 KJ/mol. The CerS1 catalytic domain experienced an opposite trend compared to the protein backbone. Yet, these residues adopted a highly compact conformation as per DCCM and DSSP analysis. Furthermore, conserved residues (SER 212, ASP 213, ALA 240, GLY 243, ASP 319) comprising the substrate shuttling machinery showed notable rigidity implying a restrained ceramide precursor access and assembly; hence, a possible inhibitory mechanism. Findings from this report would streamline a better molecular understanding of CerS1-Hsp27 interactions and decipher its potential avenue toward unexplored anti-cancer mechanisms and therapy.

Reducing non-technical losses in electricity distribution networks: Leveraging explainable AI and three lines of defence model to manage operational staff-related factors

This study presents a multidisciplinary approach involving Explainable Artificial Intelligence (ExAI) and operational risk management to reduce Non-Technical Losses (NTL) in electricity distribution. It empirically explores how the activities of employees of utility companies contribute to NTL, a phenomenon often overlooked in existing empirical research. An ensemble classification algorithm is used to analyse utility operations data, and the SHAP explainability technique establishes the predictive significance of staff activities for NTL. Subsequently, these staff activities are mapped into risk cells using the BASEL II and III operational risk definitions, and the Three Lines of Defence (3LoD) model is developed for optimizing electricity distribution. The paper makes three original contributions to the literature: first, it empirically links staff operations to NTL; second, it maps NTL causes to Basel II/III operational risk categories; and finally, to the best of the authors’ knowledge, it is the first study to use the 3LoD model for electricity distribution optimization.

Modeling the interaction of vegetation and sea level rise on barrier island evolution.

Barrier islands provide a first line of defense against ocean flooding and storm surge. Biogeomorphic interactions are recognized as important in coastal system processes, but current barrier island models are primarily dominated by physical processes. Recent research has demonstrated different biogeomorphic states that influence response to sea level rise and other disturbance. Building on this understanding, we present a cellular model utilizing biotic and abiotic processes and their interactions for barrier island evolution. Using the literature and field derived parameters, we model barrier island evolution and compare to three decades of change for Smith Island, a Virginia Coast Reserve barrier island. We conduct simulations that show the impact of biogeomorphic states on island migration under different sea level rise scenarios. We find that migration is highest in areas with low topography and light vegetation cover (i.e. disturbance reinforcing) compared to areas with greater topographic complexity and high cover of woody vegetation i.e. disturbance resisting). This study demonstrates the importance of biogeomorphic interactions for barrier island evolution with sea level rise and will aid future predictions for these important ecosystems with climate change.

On the Cultivation of National Security Education Teachers Qualities in Primary, Secondary, and Tertiary Schools in the New Era

The report of the 20th National Congress of the Communist Party of China once again emphasized the importance of national security education, clearly requiring the whole society to strengthen national security awareness and build a solid national security defense line. Under this guiding ideology, it is particularly urgent to comprehensively enhance the competence of national security education teachers in primary, secondary, and tertiary schools. By building a systematic training system, enhancing teachers professional knowledge and comprehensive literacy, and establishing a multi-level and multi-dimensional assessment mechanism, teachers teaching level and practical ability can be effectively improved. This article explores effective strategies for cultivating the competence of national security education teachers in the new era from these perspectives, in order to promote the sustainable development and innovation of national security education and ensure the in-depth promotion of national security education.

Effects of Limosilactobacillus reuteri strains PTA-126787 and PTA-126788 on intestinal barrier integrity and immune homeostasis in an alcohol-induced leaky gut model

Intestinal barrier is a first line of defense that prevents entry of various harmful substances from the lumen into the systemic environment. Impaired barrier function with consequent translocation of harmful substances into systemic circulation (“leaky gut”) is a central theme in many gastrointestinal, autoimmune, mental, and metabolic diseases. Probiotics have emerged as a promising strategy to maintain intestinal integrity and address “leaky gut”. Using in silico, in vitro and avian in vivo analyses, we previously showed that two novel L. reuteri strains, PTA-126787 (L. reuteri 3630) and PTA-126788 (L. reuteri 3632), isolated from broiler chickens possess favorable safety profiles. Consistent with a recent study, here we show that L. reuteri 3630 and 3632 are phylogenetically similar to human L. reuteri strains. Daily administration of high doses of L. reuteri 3630 and 3632 to Sprague Dawley rats for 28 days was found to be safe with no adverse effects. More importantly, administration of L. reuteri 3630 and 3632 significantly reduced markers associated with alcohol-induced leaky gut, by downregulating inflammatory cytokines and upregulating anti-inflammatory cytokines in an alcohol model of leaky gut in mice. While L. reuteri 3630 cells and supernatant showed no activation, L. reuteri 3632 cells but not supernatant showed activation of AhR, a key transcription factor that regulates gut and immune homeostasis. L. reuteri 3630 is creamish white in morphology typical of Lactobacillus species and L. reuteri 3632 displays a unique orange pigmentation, which was stable even after passaging for 480 generations. We identified a rare polyketide biosynthetic gene cluster in L. reuteri 3632 that likely encodes for the orange-pigmented secondary metabolite. Similar to L. reuteri 3632 cells, the purified orange metabolite activated AhR. All together, these data provide evidence on the phylogenetic relatedness, safety, efficacy, and one of the likely mechanisms of action of L. reuteri 3630 and 3632 for potential probiotic applications to address “leaky gut” and associated pathologies in humans.

Exploring Forgiveness through Theologically Informed Education: Lessons from Judaism

Education serves as the primary line of defense against crime and other psychological difficulties. Children exposed to adversity and emotional challenges may be susceptible to various risks, potentially leading to criminal activities. Forgiveness has been demonstrated as a healing influence in the lives of individuals who have experienced hurt and accumulated negative emotions due to life events. Understanding forgiveness from a young age, in both theory and practice, may facilitate improved relationships and psychological well-being. This article underscores the significance of forgiveness education, advocating for a culturally and theologically sensitive approach. In this article we will offer an example of integrating forgiveness education principles with insights from Judaic sources. The aim is to generate insights regarding theologically sensitive forgiveness in general by focusing on Judaism. As we demonstrate, the implications of this approach extend beyond the Jewish context, and our conclusions and recommendations are applicable to diverse cultures and religions worldwide.

Fully coupled hydromechanical study of tunnel excavation considering leachate leakage from a high water-level landfill

The Jigongshan Mountain Tunnel was constructed beneath a high water-level landfill in Shenzhen, China. Previous studies could not fully capture the hydraulic interactions between the tunnel excavation and the landfill leachate seepage. In this study, a fully coupled hydromechanical numerical model, considering the unsaturated properties and the changing permeability of the waste and geological materials, was established to simulate the landfill leakage and the tunnel excavation simultaneously. Parameter analysis was conducted to explore the effects of the configuration and dimensions of the leakage pathway and leakage points on the seepage field. Results indicate the landfill leakage has a minimal effect on tunnel displacement. The leakage width and the leakage path in the clay significantly affect the pore pressure of the tunnel. In scenarios of severe leakage, the pore pressure of the tunnel can reach as high as 0.615 MPa. Three defensive lines and the fully cover waterproofing layer were suggested for the tunnel waterproofing system under the Xiaping landfill. This research contributes valuable insights for the design and construction of subsurface structures in proximity to landfills.

Bacterial outer membrane vesicles increase polymyxin resistance in Pseudomonas aeruginosa while inhibiting its quorum sensing

The persistent emergence of multidrug-resistant bacterial pathogens is leading to a decline in the therapeutic efficacy of antibiotics, with Pseudomonas aeruginosa (P. aeruginosa) emerging as a notable threat. We investigated the antibiotic resistance and quorum sensing (QS) system of P. aeruginosa, with a particular focused on outer membrane vesicles (OMVs) and polymyxin B as the last line of antibiotic defense. Our findings indicate that OMVs increase the resistance of P. aeruginosa to polymyxin B. The overall gene transcription levels within P. aeruginosa also reveal that OMVs can reduce the efficacy of polymyxin B. However, both OMVs and sublethal concentrations of polymyxin B suppressed the transcription levels of genes associated with the QS system. Furthermore, OMVs and polymyxin B acted in concert on the QS system of P. aeruginosa to produce a more potent inhibitory effect. This suppression was evidenced by a decrease in the secretion of virulence factors, impaired bacterial motility, and a notable decline in the ability to form biofilms. These results reveal that OMVs enhance the resistance of P. aeruginosa to polymyxin B, yet they collaborate with polymyxin B to inhibit the QS system. Our research contribute to a deeper understanding of the resistance mechanisms of P. aeruginosa in the environment, and provide new insights into the reduction of bacterial infections caused by P. aeruginosa through the QS system.

Assessment of a Force Method for the Resilient Seismic Design of Special Moment-Resisting Steel Frames with Hysteretic Energy Dissipation Devices

In this paper, the authors present the results of nonlinear dynamic analyses of twelve building models designed according to a methodology based upon the force method, capacity design principles and the concept of structural fuses to achieve resilient seismic designs for special moment-resisting steel frames with hysteretic energy dissipation devices mounted on chevron steel bracing. It is demonstrated that the resilient design mechanism previously checked with pushover analyses is also attained for most studied models with nonlinear dynamic analyses using an acceleration record which is compatible with the elastic design spectrum. Also, it is corroborated that the planned second line of inelastic defense is activated if the seismic action surpasses the considered design spectrum. Based upon the obtained results, it is confirmed that it is possible to perform a resilient seismic design for the studied system under the proposed methodology, even for tall and slender buildings. Therefore, the proposed initial stiffness ratio parameters and the global design parameters previously proposed by the authors to use in a code-oriented force method can be used with confidence for the resilient seismic design of this structural system.

Construction of a rear defensive line in the Vladimir and Ivanovo regions in 1941–1943

The prepared defensive fortifications, despite technical innovations, continued to play an important role in the battles of the Great Patriotic War. In the catastrophic conditions of the autumn of 1941, the leadership of the USSR made a largely spontaneous decision to build a number of defensive lines east of Moscow. In many ways, these actions were caused by uncertainty about the outcome of the Moscow Battle. The consequence of such decisions was the construction of a defensive line on the territory of modern Vladimir and Ivanovo regions. The authors, based on archival sources and ego-documents, attempted to reconstruct the process of constructing this line of defense, and also showed the difficulties that arose during construction. Attention is drawn to the decisive importance of the efforts of local authorities and communities in the implementation of the GKO task. Most of the structures were built relying solely on local resources. The specifics of the described defensive line, as well as the fortifications built by the Soviet people east of the regions in question, were non-participation in hostilities, so it was not necessary to test the possibilities of the frontier in practice. That is why the study of defensive fortifications erected in the territories of the Vladimir and Ivanovo regions is primarily of interest as an important aspect of the daily life of the local population mobilized for these works. The analysis of sources shows great difficulties in providing workers with adequate food and work clothes, and also draws attention to the most difficult conditions in which construction took place both due to the time of year (autumn – winter 1941–1942) and the acute shortage of inventory, equipment and draft force. Подготовленные оборонительные укрепления, несмотря на технические новшества, продолжали играть важную роль в сражениях Великой Отечественной войны. В катастрофических условиях осени 1941 г. руководство СССР приняло во многом спонтанное решение о строительстве ряда оборонительных линий к востоку от Москвы. Во многом данные действия были вызваны неуверенностью в исходе Московской битвы. Следствием таких решений стало строительство оборонительного рубежа на территории современных Владимирской и Ивановской областей. Авторы на основе архивных источников и эго-документов попытались реконструировать процесс возведения этой линии обороны, а также показали сложности, которые возникли в ходе строительства. Обращается внимание на определяющее значение усилий местных властей и населений в реализации задания ГКО. Большая часть сооружений была возведена, опираясь исключительно на местные ресурсы. Спецификой описываемой оборонительной линии, как и укреплений, построенных советским народом восточнее рассматриваемых регионов, стало неучастие в боевых действиях, поэтому проверить на практике возможности рубежа не пришлось. Именно поэтому исследование оборонительных укреплений, возведенных на территориях Владимирской и Ивановской областей, в первую очередь представляет интерес как важнейший аспект повседневной жизни местного населения, мобилизованного на эти работы. Анализ источников показывает большие трудности с обеспечением трудящихся достаточным питанием и спецодеждой, а также обращает внимание на сложнейшие условия, в которых проходило строительство как ввиду времени года (осень – зима 1941–1942 гг.), так и острого недостатка инвентаря, техники и тяглой силы.

Manipulation of Macrophages: Emerging Mechanisms of Leishmaniasis.

As professional phagocytes, macrophages represent the first line of defence against invading microbial pathogens. Various cellular processes such as programmed cell death, autophagy and RNA interference (RNAi) of macrophages are involved directly in elimination or assist in elimination of invading pathogens. However, parasites, such as Leishmania, have evolved diverse strategies to interfere with macrophage cell functions, favouring their survival, growth and replication inside hostile and restrictive environments of macrophages. Therefore, identification and detailed characterization of macrophage-pathogen interactions is the key to understanding how pathogens subvert macrophage functions to support their infection and disease process. In recent years, great progress has been achieved in understanding how Leishmania affects with critical host macrophage functions. Based on latest progress and accumulating knowledge, this review exclusively focuses on macrophage-Leishmania interaction, providing an overview of macrophage cellular processes such as programmed cell death, autophagy and RNAi during Leishmania infection. Despite extensive progress, many questions remain and require further investigation.

First line of defence: Eucalyptus leaf waxes influence infection by an aggressive fungal leaf pathogen.

Leaf epicuticular waxes provide important anatomical and chemical defences against fungi that infect leaves. In this study we analysed the leaf wax composition of Eucalyptus grandis × Eucalyptus urophylla hybrids with contrasting susceptibilities to Teratosphaeria leaf blight (TLB) caused by Teratosphaeria destructans, one of the most important foliar diseases of Eucalyptus. The Eucalyptus cuticular wax was extracted from non-inoculated and inoculated genotypes with different levels of susceptibility to TLB and analysed by gas chromatography-mass spectrometry. The results showed that a triterpenoid, cycloartenol (CAS), was abundant in a resistant genotype and that hexanedioic acid content increased in the resistant genotypes in response to T. destructans infection. In contrast, palmitic acid was significantly more abundant in the inoculated highly susceptible genotype. In-vitro and in-planta T.destructans spore germination assays with pure compounds, showed that CAS and hexanedioic acid significantly inhibited spore germination. Application of these two compounds to the leaves of a susceptible host also significantly increased resistance to infection. In contrast, palmitic acid promoted spore germination and, when applied to the leaves of a resistant genotype, increased colonization by the pathogen. This is the first study providing insights into differences in the leaf wax composition of hosts with different levels of susceptibility to T. destructans. It also showed that leaf wax compounds can modulate spore germination and, ultimately, host resistance to infection.

Polysaccharide from Areca catechu L. inflorescence enhances the intestinal mucosal immunity to maintain immune homeostasis

Being the first line of defense, intestinal mucosal immunity serves as in maintaining immune homeostasis among organisms. This study investigated the impact of the areca inflorescence polysaccharide (AFP) on intestinal mucosal immunity and elucidated the mechanisms responsible for the immunomodulatory effects of AFP. The immunosuppression mouse model was established using the cyclophosphamide. The intestinal mucosal status was evaluated based on the intestinal integrity, chemical and mucosal immune barriers, and intestinal flora. According to the findings, AFP enhances intestinal integrity by up-regulating the expression of tight junction proteins and reinforcing the chemical barrier through increased mucin-2, β-defensins, and SIgA expression and secretion. Furthermore, AFP restores the mucosal immune barrier by regulating immune cells within Peyer's patches and lamina propria. AFP also reverses the intestinal flora balance and regulates its metabolism. Additionally, AFP effectively modulates the immune response in the spleen and peripheral blood. Together, these results indicated that AFP repairs mucosal damage and restores mucosal immunity, thereby preserving the immune homeostasis of organisms.