Zhen-Wu-Tang ameliorates lupus nephritis by diminishing renal tissue-resident memory CD8+ T cells via suppressing IL-15/STAT3 pathway.

Zhen-Wu-Tang (ZWT), a conventional herbal mixture, has been recommended for treating lupus nephritis (LN) in clinic. However, its mechanisms of action remain unknown. Here we aimed to define the immunological mechanisms underlying the effects of ZWT on LN and to determine whether it affects renal tissue-resident memory T (TRM) cells. Murine LN was induced by a single injection of pristane, while in vitro TRM cells differentiated with IL-15/TGF-ß. We found that ZWT or mycophenolate mofetil treatment significantly ameliorated kidney injury in LN mice by decreasing 24-h urine protein, Scr and anti-dsDNA Ab. ZWT also improved renal pathology and decreased IgG and C3 depositions. In addition, ZWT down-regulated renal Desmin expression. Moreover, it lowered the numbers of CD8+ TRM cells in kidney of mice with LN while decreasing their expression of TNF-α and IFN-γ. Consistent with in vivo results, ZWT-containing serum inhibited TRM cell differentiation induced by IL-15/TGF-ß in vitro. Mechanistically, it suppressed phosphorylation of STAT3 and CD122 （IL2/IL-15Rß）expression in CD8+ TRM cells. Importantly, ZWT reduced the number of total F4/80+CD11b+ and CD86+, but not CD206+, macrophages in the kidney of LN mice. Interestingly, ZWT suppressed IL-15 protein expression in macrophages in vivo and in vitro. Thus, we have provided the first evidence that ZWT decoction can be used to improve the outcome of LN by reducing CD8+ TRM cells via inhibition of IL-15/IL-15R /STAT3 signaling.

Scaffold-Based Poly(Vinylidene Fluoride) and Its Copolymers: Materials, Fabrication Methods, Applications, and Perspectives.

Tissue engineering involves implanting grafts into damaged tissue sites to guide and stimulate the formation of new tissue, which is an important strategy in the field of tissue defect treatment. Scaffolds prepared in vitro meet this requirement and are able to provide a biochemical microenvironment for cell growth, adhesion, and tissue formation. Scaffolds made of piezoelectric materials can apply electrical stimulation to the tissue without an external power source, speeding up the tissue repair process. Among piezoelectric polymers, poly(vinylidene fluoride) (PVDF) and its copolymers have the largest piezoelectric coefficients and are widely used in biomedical fields, including implanted sensors, drug delivery, and tissue repair. This paper provides a comprehensive overview of PVDF and its copolymers and fillers for manufacturing scaffolds as well as the roles in improving piezoelectric output, bioactivity, and mechanical properties. Then, common fabrication methods are outlined such as 3D printing, electrospinning, solvent casting, and phase separation. In addition, the applications and mechanisms of scaffold-based PVDF in tissue engineering are introduced, such as bone, nerve, muscle, skin, and blood vessel. Finally, challenges, perspectives, and strategies of scaffold-based PVDF and its copolymers in the future are discussed.

The TOPK inhibitor HI-TOPK-032 enhances CAR T-cell therapy of hepatocellular carcinoma by upregulating memory T cells.

Chimeric antigen receptor (CAR) T cells are emerging as an effective antitumoral therapy. However, their therapeutic effects on solid tumors are limited due to their short survival time and the immunosuppressive tumor microenvironment. Memory T cells respond more vigorously and persist longer than their naive/effector counterparts. Therefore, promoting CAR T-cell development into memory T cells could further enhance their antitumoral effects. HI-TOPK-032 is a TOPK-specific inhibitor that moderately represses some types of tumors. However, it is unknown whether HI-TOPK-032 works on hepatocellular carcinoma (HCC) and whether it impacts antitumoral immunity. Using both subcutaneous and orthotopic xenograft tumor models of two human HCC cell lines, Huh-7 and HepG2, we found that HI-TOPK-032 significantly improved proliferation/persistence of CD8+ CAR T cells, as evidenced by an increase in CAR T-cell counts or frequency of Ki-67+CD8+ cells and a decrease in PD-1+LAG-3+TIM-3+CD8+ CAR T cells in vivo. Although HI-TOPK-032 did not significantly suppress HCC growth, it enhanced the capacity of CAR T cells to inhibit tumor growth. Moreover, HI-TOPK-032 augmented central memory CD8+ T cell (TCM) frequency while increasing eomesodermin expression in CD8+ CAR T cells in tumor-bearing mice. Moreover, it augmented CD8+ CAR TCM cells in vitro and reduced their expression of immune checkpoint molecules. Finally, HI-TOPK-032 inhibited mTOR activation in CAR T cells in vitro and in tumors, whereas overactivation of mTOR reversed the effects of HI-TOPK-032 on CD8+ TCM cells and tumor growth. Thus, our studies have revealed mechanisms underlying the antitumoral effects of HI-TOPK-032 while advancing CAR T-cell immunotherapy.

Biofabrication of biomimetic undulating microtopography at the dermal-epidermal junction and its effects on the growth and differentiation of epidermal cells.

The undulating microtopography located at the junction of the dermis and epidermis of the native skin is called rete ridges (RRs), which plays an important role in enhancing keratinocyte function, improving skin structure and stability, and providing three-dimensional (3D) microenvironment for skin cells. Despite some progress in recent years, most currently designed and manufactured tissue-engineered skin models still cannot replicate the RRs, resulting in a lack of biological signals in the manufactured skin models. In this study, a composite manufacturing method including electrospinning, 3D printing, and functional coating was developed to produce the epidermal models with RRs. Polycaprolactone (PCL) nanofibers were firstly electrospun to mimic the extracellular matrix environment and be responsible for cell attachment. PCL microfibers were then printed onto top of the PCL nanofibers layer by 3D printing to quickly prepare undulating microtopography and finally the entire structures were dip-coated with gelatin hydrogel to form a functional coating layer. The morphology, chemical composition, and structural properties of the fabricated models were studied. The results proved that the multi-process composite fabricated models were suitable for skin tissue engineering. Live and dead staining, cell counting kit-8 (CCK-8) as well as histology (haematoxylin and eosin (HE) methodology) and immunofluorescence (primary and secondary antibodies combination assay) were used to investigate the viability, metabolic activity, and differentiation of skin cells forin vitroculturing.In vitroresults showed that each model had high cell viability, good proliferation, and the expression of differentiation marker. It was worth noting that the sizes of the RRs affected the cell growth status of the epidermal models. In addition, the unique undulation characteristics of the epidermal-dermal junction can be reproduced in the developed epidermal models. Overall, thesein vitrohuman epidermal models can provide valuable reference for skin transplantation, screening and safety evaluation of drugs and cosmetics.

Interactions between CNS and immune cells in tuberculous meningitis.

The central nervous system (CNS) harbors its own special immune system composed of microglia in the parenchyma, CNS-associated macrophages (CAMs), dendritic cells, monocytes, and the barrier systems within the brain. Recently, advances in the immune cells in the CNS provided new insights to understand the development of tuberculous meningitis (TBM), which is the predominant form of Mycobacterium tuberculosis (M.tb) infection in the CNS and accompanied with high mortality and disability. The development of the CNS requires the protection of immune cells, including macrophages and microglia, during embryogenesis to ensure the accurate development of the CNS and immune response following pathogenic invasion. In this review, we summarize the current understanding on the CNS immune cells during the initiation and development of the TBM. We also explore the interactions of immune cells with the CNS in TBM. In the future, the combination of modern techniques should be applied to explore the role of immune cells of CNS in TBM.

Mechanisms underlying the efficacy and limitation of dopa and tetrahydrobiopterin therapies for the deficiency of GTP cyclohydrolase 1 revealed in a novel mouse model.

Dopa and tetrahydrobiopterin (BH4) supplementation are recommended therapies for the dopa-responsive dystonia caused by GTP cyclohydrolase 1 (GCH1, also known as GTPCH) deficits. However, the efficacy and mechanisms of these therapies have not been intensively studied yet. In this study, we tested the efficacy of dopa and BH4 therapies by using a novel GTPCH deficiency mouse model, Gch1KI/KI, which manifested infancy-onset motor deficits and growth retardation similar to the patients. First, dopa supplementation supported Gch1KI/KI mouse survival to adulthood, but residual motor deficits and dwarfism remained. Interestingly, RNAseq analysis indicated that while the genes participating in BH4 biosynthesis and regeneration were significantly increased in the liver, no significant changes were observed in the brain. Second, BH4 supplementation alone restored the growth of Gch1KI/KI pups only in early postnatal developmental stage. High doses of BH4 supplementation indeed restored the total brain BH4 levels, but brain dopamine deficiency remained. While total brain TH levels were relatively increased in the BH4 treated Gch1KI/KI mice, the TH in the striatum were still almost undetectable, suggesting differential BH4 requirements among brain regions. Last, the growth of Gch1KI/KI mice under combined therapy outperformed dopa or BH4 therapy alone. Notably, dopamine was abnormally high in more than half, but not all, of the treated Gch1KI/KI mice, suggesting the existence of variable synergetic effects of dopa and BH4 supplementation. Our results provide not only experimental evidence but also novel mechanistic insights into the efficacy and limitations of dopa and BH4 therapies for GTPCH deficiency.

Mini review of photoacoustic clinical imaging: a noninvasive tool for disease diagnosis and treatment evaluation.

Significance: Photoacoustic (PA) imaging is an imaging modality that integrates anatomical, functional, metabolic, and histologic insights. It has been a hot topic of medical research and draws extensive attention. Aim: This review aims to explore the applications of PA clinical imaging in human diseases, highlighting recent advancements. Approach: A systemic survey of the literature concerning the clinical utility of PA imaging was conducted, with a particular focus on its application in tumors, autoimmune diseases, inflammatory conditions, and endocrine disorders. Results: PA imaging is emerging as a valuable tool for human disease investigation. Information provided by PA imaging can be used for diagnosis, grading, and prognosis in multiple types of tumors including breast tumors, ovarian neoplasms, thyroid nodules, and cutaneous malignancies. PA imaging facilitates the monitoring of disease activity in autoimmune and inflammatory diseases such as rheumatoid arthritis, systemic sclerosis, arteritis, and inflammatory bowel disease by capturing dynamic functional alterations. Furthermore, its unique capability of visualizing vascular structure and oxygenation levels aids in assessing diabetes mellitus comorbidities and thyroid function. Conclusions: Despite extant challenges, PA imaging offers a promising noninvasive tool for precision disease diagnosis, long-term evaluation, and prognosis anticipation, making it a potentially significant imaging modality for clinical practice.

Endoplasmic reticulum stress interferes with the development of type 1 regulating T cells.

BACKGROUND: A variety of stimuli can cause endoplasmic reticulum (ER) stress, which is a common cellular reaction. It is not yet clear how ER stress contributes to the pathogenesis of ulcerative colitis (UC). The deregulation of regulatory T cell (Treg) is associated with UC. The goal of this study is to shed light on how ER stress affects Treg's development. METHODS: CD4+ CD25- T cells were isolated from blood samples collected from UC patients and healthy control (HC) subjects. ER stress-associated molecule expression in CD4+ CD25- T cell was assessed by RNA sequencing and RT-qPCR. RESULTS: The presence of ER stress in peripheral CD4+ CD25- T cells was observed in patients with UC compared to HC subjects. The induction of ER stress in HC CD4+ CD25- T cells by polyclonal activation was made worse by the presence of 3-methyl-4-nitrophenol (MNP; a common environmental pollutant). Exposure to MNP in culture resulted in an increase in the expression of ring finger protein 20 (Rnf20) in CD4+ CD25- T cells. The synergistic effects of MNP and ER stress on the reduction of IL-10 levels in CD4+ CD25- T cells are mediated by Rnf20, which prevents the development of Tr1 cells. Inhibition of Rnf20 resulted in the development of Tr1 cells from CD4+ CD25- T cells in UC patients. CONCLUSIONS: The synergistic effects of ER stress and MNP interfere with the development of Tr1 cells. The development of Tr1 from CD4+ CD25- T cells in patients with UC is re-established by Rnf20 inhibition.

Direct Detection of Tobacco Mosaic Virus in Infected Plants with SERS-Sensing Hydrogels.

The impact of plant pathogens on global crop yields is a major societal concern. The current agricultural diagnostic paradigm involves either visual inspection (inaccurate) or laboratory molecular tests (burdensome). While field-ready diagnostic methods have advanced in recent years, issues remain with detection of presymptomatic infections, multiplexed analysis, and requirement for in-field sample processing. To overcome these issues, we developed surface-enhanced Raman scattering (SERS)-sensing hydrogels that detect pathogens through simple contact with a leaf. In this work, we developed a novel reagentless SERS sensor for the detection of tobacco mosaic virus (TMV) and embedded it in an optimized hydrogel material to produce sensing hydrogels. To test the diagnostic application of our sensing hydrogels, we demonstrate their use to detect TMV infection in tobacco plants. This technology has the potential to shift the current agricultural diagnostic paradigm by offering a field-deployable tool for presymptomatic and multiplexed molecular identification of pathogens.

Methotrexate and electrostimulation cooperate to alleviate the relapse of psoriasiform skin inflammation by suppressing memory T cells.

Methotrexate (MTX) is an immunosuppressant used to treat autoimmune diseases, including psoriasis. However, like other immunosuppressants, MTX alone does not prevent their recurrence. Electrostimulation (ES) has been utilized to treat some inflammatory disorders without any major side-effect. But it remains unknown if ES alone, or together with MTX, ameliorates autoimmune disease relapse: a sticky medical problem. In particular, the mechanisms underlying ES action remain unclear. The objective of this study was to determine an impact of ES and/or MTX on psoriasis relapse and their potential cooperation. We found that regional ES, but not MTX, ameliorated psoriasiform skin inflammation recurrence. Interestingly, treatment with both MTX and ES further prevented psoriasis recurrence compared to ES alone. Moreover, ES downregulated potassium channel Kv1.3 on T-cells and reduced CD4+/CD8+ effector memory (TEM) and CD8+ skin-resident memory T (TRM) cells, while ES plus MTX further decreased CD8+ TEM/TRM cells compared to ES alone. However, ES failed to further attenuate psoriasis recurrence or suppress T cell memory in Kv1.3-deficient mice, whereas lack of Kv1.3 itself ameliorated psoriasis relapse by shrinking T cell memory pool. Importantly, ES moderately inhibited T-cell proliferation in vitro. ES also reduced human CD8+ TRM cells and attenuated human skin lesions in humanized mice grafted with lesional skin from patients with recurrent psoriasis, with an enhanced efficacy in mice treated with both ES and MTX. Thus, ES and MTX cooperated to prevent psoriasis relapse by reducing T-cell memory via targeting potassium channel Kv1.3. Our studies may be implicated for treating human psoriasis.

A novel portable in situ printer for hydrogel multi-structure molding and cell printing.

Skin lesions not only disrupt appearance and barrier functionality but also lead to severe microbial infections and immune-inflammatory responses, seriously affect physical and mental health. In situ printing involves the direct deposition of bio-ink to create or repair damaged tissues or organs within a clinical setting. In this study, we designed and fabricated a novel portable in situ printer. This handheld instrument exhibits excellent printing performance, allowing hydrogels to be patterned and molded on surfaces according to specific requirements. By utilizing a dual-component hydrogels co-printing approach with high and low viscosities, we achieved in situ cell-laden printing using low-viscosity hydrogel. This demonstrates the advantages of the device in maintaining cell viability and achieving hydrogel structuring. This approach opens up the possibilities for the efficient encapsulation of active components such as drugs, proteins, and cells, enabling controlled macro- and micro-structuring of hydrogels. This breakthrough finding highlights the potential of our technical approach in dermatological treatment and wound repair, by dynamically adapting and regulating microenvironments in conjunction with hydrogel scaffolds and cell reparative impetus.

Phosphatidylserine promotes immunotherapy for airway allergy.

Type 1 regulatory T cells (Tr1 cells) play an important role in the maintenance of the immune homeostasis in the body. The induction of Tr1 cell is to be further investigated. The interaction of phosphatidylserine (PS) with TIM3 has immune regulation functions. The objective of this study is to elucidate the role of PS-TIM3 signals in inducing Tr1 cells. In this study, mice were treated using PS or specific immunotherapy by nasal instillation. A murine model of allergic rhinitis was developed using ovalbumin as a specific antigen. We found that PS-containing nasal instillation induced Tr1 cells in the airway tissues. PS promoted gene activities associated with IL-10 through activation of TIM3 in CD4+ T cells. TIM3 mediated the effects of PS on inducing Tr1 cells, in which the TIM3- PI3K-AKT pathway played a critical role. PS boosted allergen-specific immunotherapy by inducing specific antigen Tr1 cell generation. Concomitant administration of PS and SIT resulted in better therapeutic effects on AR. In conclusion, the data demonstrate that PS can promote the specific immunotherapy for AR through inducing antigen specific Tr1 cells in the airway tissues.

Semaphorin 3 a restores the ability of type 1 regulatory T cells to suppress food allergy.

Food allergy (FA) is a common immune disorder that involves dysfunctional immune regulation. More remedies for restoring immune regulation are necessary. Semaphorin 3 A (Sema3a) is a secreted protein of the semaphorin family, which plays a role in immune responses at all stages. The objective of this study is to gain an understanding of how Sema3a can restore the immune regulatory abilities of type 1 regulatory T cells (Tr1 cells). In this study, blood samples were taken from patients with FA. Tr1 cells were purified from blood samples using flow cytometry cell sorting, using LAG3 and CD49b as surface markers. RNA sequencing was employed to examine the characteristics of Tr1 cells. We observed an exaggerated increase in ER stress in peripheral Tr1 cells of FA patients. Enforced expression of spliced X-box protein-1 (XBP1s, one of the key molecules in ER stress) resulted in suppression of interleukin (IL)-10 expression in CD4+ T cells. Eukaryotic initiation factor 2a (eIF2a) mediated the effects of XBP1 on suppressing IL-10 expression in Tr1 cells. The use of Sema3a resulted in a decrease in ER stress, and an increase in IL-10 expression in Tr1 cells of FA patients. Sema3a administration reduced experimental FA by increasing the number of Tr1 cells. In conclusion, IL-10 expression in Tr1 cells is disturbed by ER stress. Sema3a treatment restores the expression of IL-10 and the immunosuppressive capability of Tr1 cells.

Enterococcus faecium HDRsEf1 Promotes Systemic Th1 Responses and Enhances Resistance to SalmonellaTyphimurium Infection.

The gut microbiota is known to regulate the immune system and thereby influence susceptibility to infection. In this study, we observed that the administration of Enterococcus faecium HDRsEf1 (HDRsEf1) led to an improvement in the development of the immune system. This was evidenced by an increase in both the spleen index and the area of spleen white pulp. Specifically, the proportion of T helper (Th) 1 cells and the production of IFN-γ and IL-12 were significantly increased in the spleens of mice treated with HDRsEf1. In agreement with the in vivo results, we found that Th1-related cytokines, including IFN-γ and IL-12p70, were strongly induced in splenocytes treated with HDRsEf1. In addition, Th1 cell activation and high-level secretion of IL-12p70 were also confirmed by coculture of CD4+ T cells with bone marrow-derived dendritic cells treated with HDRsEf1. Moreover, the employment of HDRsEf1 was identified to augment resilience against systemic infection provoked by S. Typhimurium and stimulate the expression of the genes for TNFα and iNOS in the initial stage of infection, signifying that reinforced Th1 cells and IL-12 might activate macrophages for antibacterial safeguards. In summary, our study suggests that HDRsEf1 could act as an effective immunobiotic functional agent, promoting systemic Th1 immunological responses and priming defenses against infection.

High-frame-rate reconfigurable diffractive neural network based on superpixels.

The existing implementations of reconfigurable diffractive neural networks rely on both a liquid-crystal spatial light modulator and a digital micromirror device, which results in complexity in the alignment of the optical system and a constrained computational speed. Here, we propose a superpixel diffractive neural network that leverages solely a digital micromirror device to control the neuron bias and connection. This approach considerably simplifies the optical system and achieves a computational speed of 326 Hz per neural layer. We validate our method through experiments in digit classification, achieving an accuracy of 82.6%, and action recognition, attaining a perfect accuracy of 100%. Our findings demonstrate the effectiveness of the superpixel diffractive neural network in simplifying the optical system and enhancing computational speed, opening up new possibilities for real-time optical information processing applications.

Systematic Study of Aluminum Corrosion in Ionic Liquid Electrolytes for Sodium-Ion Batteries: Impact of Temperature and Concentration.

The development of sodium-ion batteries utilizing sulfonylamide-based electrolytes is significantly encumbered by the corrosion of the Al current collector, resulting in capacity loss and poor cycling stability. While ionic liquid electrolytes have been reported to suppress Al corrosion, a recent study found that pitting corrosion occurs even when ionic liquids are employed. This study investigates the effects of temperature and Na salt concentration on the Al corrosion behavior in different sulfonylamide-based ionic liquid electrolytes for sodium-ion batteries. In the present work, cyclic voltammetry measurements and scanning electron microscopy showed that severe Al corrosion occurred in ionic liquids at high temperatures and low salt concentrations. X-ray photoelectron spectroscopy was employed to identify the different elemental components and verify the thickness of the passivation layer formed under varied salt concentrations and temperatures. The differences in the corrosion behaviors observed under the various conditions are ascribed to the ratio of free [FSA]- to Na+-coordinating [FSA]- in the electrolyte and the stability of the newly formed passivation layer. This work aims at augmenting the understanding of Al corrosion behavior in ionic liquid electrolytes to develop advanced batteries.

Punicalagin alleviates the hyperproliferation of keratinocytes in psoriasis through inhibiting SKP2 expression.

Psoriasis is a chronic inflammatory skin disorder characterized by abnormal keratinocytes proliferation and multiple immune cells infiltration in the dermis and epidermis. Although most psoriasis-related researches have been concentrated on the interleukin-23 (IL-23)/interleukin-17 (IL-17) axis, new data suggest that keratinocytes also play a pivotal role in psoriasis. Previously, we found that punicalagin (PUN), a bioactive ellagitannin extracted from Pericarpium Granati (the pericarpium of Punica granatum L.), exerts a therapeutic effect on psoriasis. However, the underlying mechanism, especially its potential modulatory effect on keratinocytes, remains obscure. Our study aims to reveal the potential regulatory effect and its underlying cellular mechanism of PUN on the hyperproliferation of keratinocytes. We used tumor necrosis factor α (TNF-α), IL-17A and interleukin-6 (IL-6) to induce abnormal proliferation of HaCaT cells (Human Keratinocytes Cells) in vitro. Then, we evaluated the effects of PUN through MTT assay, EdU staining and cell cycle detection. Finally, we explored the underlying cellular mechanisms of PUN via RNA-sequencing, WB in vitro and in vivo. Here, we found that PUN can directly and dose-dependently decrease TNF-α, IL-17A and IL-6-induced abnormal proliferation of HaCaT cells in vitro. Mechanically, PUN suppresses the hyperproliferation of keratinocytes through repressing S-phase kinase-associated protein 2 (SKP2) expression in vitro and in vivo. Moreover, overexpression of SKP2 can partly abolish PUN-mediated inhibition of aberrantly proliferative keratinocytes. These results illustrate that PUN can reduce the severity of psoriasis through directly repressing SKP2-mediated abnormal proliferation of keratinocytes, which gives new insight into the therapeutic mechanism of PUN on psoriasis. Moreover, these findings imply that PUN might be a promising drug candidate for the treatment of psoriasis.

Fecal microbiota transplantation improves chicken growth performance by balancing jejunal Th17/Treg cells.

BACKGROUND: Intestinal inflammation has become a threatening concern in chicken production worldwide and is closely associated with Th17/Treg cell imbalance. Several studies described that gut microbiota is significantly implicated in chicken growth by modulating intestinal immune homeostasis and immune cell differentiation. Whether reshaping gut microbiota by fecal microbiota transplantation (FMT) could improve chicken growth by balancing Th17/Treg cells is an interesting question. RESULTS: Here, the chickens with significantly different body weight from three different breeds (Turpan cockfighting × White Leghorn chickens, white feather chickens, and yellow feather chickens) were used to compare Th17 and Treg cells. qPCR and IHC staining results indicated that Th17 cell-associated transcriptional factors Stat3 and rorγt and cytokines IL-6, IL-17A, and IL-21 were significantly (P < 0.05) higher in the jejunum of low body weight chickens, while Treg cell-associated transcriptional factor foxp3 and cytokines TGF-ß and IL-10 were significantly (P < 0.05) lower in the jejunum of low body weight chickens, indicating imbalanced Th17/Treg cells were closely related to chicken growth performance. Transferring fecal microbiota from the healthy donor with better growth performance and abundant Lactobacillus in feces to 1-day-old chicks markedly increased growth performance (P < 0.001), significantly decreased Th17 cell-associated transcriptional factors and cytokines, and increased Treg cell-associated transcriptional factors and cytokines in the jejunum (P < 0.05). Furthermore, FMT increased the abundance of Lactobacillus (FMT vs Con; 84.98% vs 66.94%). Besides, the metabolites of tryptophan including serotonin, indole, and 5-methoxyindoleacetate were increased as well, which activated their receptor aryl-hydrocarbon-receptor (AhR) and expressed more CYP1A2 and IL-22 to maintain Th17/Treg cell balance and immune homeostasis. CONCLUSION: These findings suggested that imbalanced Th17/Treg cells decreased chicken growth performance, while FMT-reshaped gut microbiota, i.e., higher Lactobacilli, increased chicken growth performance by balancing Th17/Treg cells. Video Abstract.

The transcription factor XBP1 in dendritic cells promotes the TH2 cell response in airway allergy.

Dendritic cells (DCs) that express T cell immunoglobulin domain molecule-4 (TIM4), a cell surface receptor for phosphatidylserine, induce T helper 2 (TH2) cell responses and allergic reactions. We elucidated the role of the transcription factor X-box-binding protein-1 (XBP1) in the induction of the TH2 cell response through its role in generating TIM4+ DCs. We found that XBP1 was required for TIM4 mRNA and protein expression in airway DCs in response to the cytokine interleukin-2 (IL-2) and that this pathway was required for TIM4 expression on DCs in response to the allergens PM2.5 and Derf1. The IL-2-XBP1-TIM4 axis in DCs contributed to Derf1/PM2.5-induced, aberrant TH2 cell responses in vivo. An interaction between the guanine nucleotide exchange factor Son of sevenless-1 (SOS1) and the GTPase RAS promoted XBP1 and TIM4 production in DCs. Targeting the XBP1-TIM4 pathway in DCs prevented or alleviated experimental airway allergy. Together, these data suggest that XBP1 is required for TH2 cell responses by inducing the development of TIM4+ DCs, which depends on the IL-2-XBP1-SOS1 axis. This signaling pathway provides potential therapeutic targets for the treatment of TH2 cell-dependent inflammation or allergic diseases.

Corrigendum: Polyphyllin I suppresses the gastric cancer growth by promoting cancer cell ferroptosis.

[This corrects the article DOI: 10.3389/fphar.2023.1145407.].