Intervention Research of Narrative Nursing on the Psychological Problems of the Caregivers Under the Normalization of the Epidemic.

Objective: The research aims to investigate the impact of narrative nursing on the psychological well-being of nursing personnel in the context of the normalization of epidemic. Methods: A cohort of 170 frontline nursing staff at our institution was selected for this clinical study from January 1st to October 31st of 2023. The Symptom Checklist-90 (SCL-90) was employed to evaluate the psychological health of these frontline nursing personnel, compared to the standard norms for nurses in mainland China. Employing a randomized selection method, the cohort was divided into two groups: a control group (85 cases) receiving conventional nursing care and a research group (85 cases) receiving narrative nursing care. The duration of nursing intervention in both groups was set at 12 weeks. Various aspects of psychological well-being, work-related stress, psychological resilience, post-traumatic stress disorder, occupational burnout, job satisfaction, and coping strategies were assessed both before and after the nursing intervention. Results: Among the positive projects of 170 frontline nursing personnel, 32 exhibited positive symptoms, resulting in a positive rate of 18.82%. With the exception of the paranoia dimension score, the scores for other dimensions in the SCL-90 scale within the clinical group were notably higher than those observed in the norm group (P < .05). Among the ten items with the highest frequency of positive symptoms, anxiety, obsessive-compulsive symptoms, and hostility were identified as the most prevalent psychological health issues among frontline nursing personnel. Post-nursing intervention, the research group exhibited lower scores in dimensions other than paranoia in the SCL-90 scale compared to the control group (P < .05). The research group also displayed lower scores in SAS, SDS, SRQ, PCL-C, MBI-HSS and higher scores in CD-RISC and JWS post-intervention (P < .05). In the post-nursing intervention phase, the research group demonstrated lower scores in negative coping and higher scores in positive coping as per the SCSQ scale in comparison to the control group (P < .05). Conclusions: Amidst the ongoing normalization of the epidemic, the psychological well-being of frontline nursing staff was lower than the established norms for nurses in mainland China. Notably, somatization, anxiety, and depression emerged as predominant manifestations. Narrative nursing was identified as an effective intervention to enhance nursing personnel's psychological well-being and coping strategies, ultimately regulating negative emotions, reducing post-traumatic stress disorder and occupational burnout, reducing stress levels, and enhancing job satisfaction and psychological resilience.

Multi-omics reveals the testosterone promotion effect mechanism of Cordyceps Sobolifera on Leydig cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Cordyceps sobolifera (CS) has been traditionally utilized as an ethnic remedy for various health conditions, including chronic kidney diseases, anti-fatigue interventions, and management of chronic inflammation. Notably, CS is recognized for its substantial content of bioactive compounds, among which nucleosides prominently feature as constituents with diverse therapeutic advantages. AIM OF THE STUDY: This study aims to investigate the effects of CS on testosterone secretion in Leydig cells and explore the underlying mechanism. MATERIALS AND METHODS: Leydig cells were isolated from rat testes to establish a primary rat Leydig cells model. Cell proliferation and testosterone secretion were assessed via the methyl-piperidino-pyrazole (MTT) assay and enzyme-linked immunosorbent assay (ELISA), respectively. Samples earmarked for RNA sequencing (RNA-Seq) analysis facilitated the identification of significantly differentially expressed genes (DEGs), and we conducted Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotation and enrichment analyses. The veracity of our findings was validated through quantitative real time polymerase chain reaction (qRT-PCR) and western blotting. RESULTS: The results showed that CS and guanosine could promote Leydig cell proliferation and bolster testosterone secretion. Our integrative analysis of metabolomics and transcriptomics has unveiled the potential mechanisms governing testosterone synthesis. Specifically, metabolomics has illuminated striking correlations within cholesterol metabolism, and bile secretion. Concurrently, transcriptomics has underscored the pivotal roles played by the cyclic adenosine monophosphate (cAMP) signaling pathway and steroid hormone biosynthesis. Furthermore, our investigation has demonstrated CS's aptitude in elevating the expression of proteins and genes. Notably, our findings have elucidated that these effects can be mitigated by protein kinase A (PKA) and adenylate cyclase (AC) specific inhibitors. CONCLUSION: This study delineates the cAMP-PKA pathways as plausible mechanisms underpinning the testosterone-enhancing properties of CS, with guanosine emerging as a fundamental bioactive constituent.

A Review of Gut Microbiota-Derived Metabolites in Tumor Progression and Cancer Therapy.

Gut microbiota-derived metabolites are key hubs connecting the gut microbiome and cancer progression, primarily by remodeling the tumor microenvironment and regulating key signaling pathways in cancer cells and multiple immune cells. The use of microbial metabolites in radiotherapy and chemotherapy mitigates the severe side effects from treatment and improves the efficacy of treatment. Immunotherapy combined with microbial metabolites effectively activates the immune system to kill tumors and overcomes drug resistance. Consequently, various novel strategies have been developed to modulate microbial metabolites. Manipulation of genes involved in microbial metabolism using synthetic biology approaches directly affects levels of microbial metabolites, while fecal microbial transplantation and phage strategies affect levels of microbial metabolites by altering the composition of the microbiome. However, some microbial metabolites harbor paradoxical functions depending on the context (e.g., type of cancer). Furthermore, the metabolic effects of microorganisms on certain anticancer drugs such as irinotecan and gemcitabine, render the drugs ineffective or exacerbate their adverse effects. Therefore, a personalized and comprehensive consideration of the patient's condition is required when employing microbial metabolites to treat cancer. The purpose of this review is to summarize the correlation between gut microbiota-derived metabolites and cancer, and to provide fresh ideas for future scientific research.

Transcriptome analysis reveals important regulatory genes and pathways for tuber color variation in Pinellia ternata (Thunb.) Breit.

During the growth of Pinellia ternata (Thunb.) Breit. (P. ternata), the violet-red skin was occasionally produced spontaneously under natural cultivation. However, the specific mechanism leading to the color change is still unclear. This study performed transcriptomes in violet-red and pale-yellow skin and their peeled tubers of P. ternata, and the total flavonoids and anthocyanin contents were also determined. The results showed that the majority of genes involved in anthocyanin production were considerably increased in the violet-red skin of P. ternata tuber compared to the pale-yellow skin. Especially, phenylalanine ammonia-lyase (PAL) and chalcone synthase (CHS) showed a remarkable increase in gene expression levels. Notably, shikimate O-hydroxycinnamoyltransferase (HCT), naringenin 3-dioxygenase (F3H), flavanone 4-reductase (DFR), and anthocyanidin synthase (ANS) were explicitly expressed in violet-red skin of P. ternata tuber, while undetectable in pale-yellow skin. The upregulation of these genes may explain the accumulation of anthocyanins, which forms the violet-red skin of P. ternata tuber. The transcription factors, including C2H2, bZIP, ERF, GATA, bHLH, C3H, NAC, MYB-related, and MYB families, might trigger the skin color change in P. ternata. The entire anthocyanin content in the violet-red skin of P. ternata tuber was 71.10 µg/g, and pale-yellow skin was 7.74 µg/g. According to phenotypic and transcriptome results, the elevated expression levels of genes linked to the synthesis of anthocyanins considerably contributed to the violet-red skin alterations in P. ternata tuber. This study provides a new understanding of the formation of the violet-red skin, lays a theoretical foundation for the cultivation of unique varieties of P. ternata, and provides transcriptome data for further study of the differences between different colors of P. ternata.

Breast cancer cell-derived extracellular vesicles promote CD8+ T cell exhaustion via TGF-ß type II receptor signaling.

Cancer immunotherapies have shown clinical success in various types of tumors but the patient response rate is low, particularly in breast cancer. Here we report that malignant breast cancer cells can transfer active TGF-ß type II receptor (TßRII) via tumor-derived extracellular vesicles (TEV) and thereby stimulate TGF-ß signaling in recipient cells. Up-take of extracellular vesicle-TßRII (EV-TßRII) in low-grade tumor cells initiates epithelial-to-mesenchymal transition (EMT), thus reinforcing cancer stemness and increasing metastasis in intracardial xenograft and orthotopic transplantation models. EV-TßRII delivered as cargo to CD8+ T cells induces the activation of SMAD3 which we demonstrated to associate and cooperate with TCF1 transcription factor to impose CD8+ T cell exhaustion, resulting in failure of immunotherapy. The levels of TßRII+ circulating extracellular vesicles (crEV) appears to correlate with tumor burden, metastasis and patient survival, thereby serve as a non-invasive screening tool to detect malignant breast tumor stages. Thus, our findings not only identify a possible mechanism by which breast cancer cells can promote T cell exhaustion and dampen host anti-tumor immunity, but may also identify a target for immune therapy against the most devastating breast tumors.

USP8 promotes cancer progression and extracellular vesicle-mediated CD8+ T cell exhaustion by deubiquitinating the TGF-ß receptor TßRII.

TGF-ß signaling is a key player in tumor progression and immune evasion, and is associated with poor response to cancer immunotherapies. Here, we identified ubiquitin-specific peptidase 8 (USP8) as a metastasis enhancer and a highly active deubiquitinase in aggressive breast tumors. USP8 acts both as a cancer stemness-promoting factor and an activator of the TGF-ß/SMAD signaling pathway. USP8 directly deubiquitinates and stabilizes the type II TGF-ß receptor TßRII, leading to its increased expression in the plasma membrane and in tumor-derived extracellular vesicles (TEVs). Increased USP8 activity was observed in patients resistant to neoadjuvant chemotherapies. USP8 promotes TGF-ß/SMAD-induced epithelial-mesenchymal transition (EMT), invasion, and metastasis in tumor cells. USP8 expression also enables TßRII+ circulating extracellular vesicles (crEVs) to induce T cell exhaustion and chemoimmunotherapy resistance. Pharmacological inhibition of USP8 antagonizes TGF-ß/SMAD signaling, and reduces TßRII stability and the number of TßRII+ crEVs to prevent CD8+ T cell exhaustion and to reactivate anti-tumor immunity. Our findings not only reveal a novel mechanism whereby USP8 regulates the cancer microenvironment but also demonstrate the therapeutic advantages of engineering USP8 inhibitors to simultaneously suppress metastasis and improve the efficacy of cancer immunotherapy.

Purple sweet potato anthocyanin extract regulates redox state related to gut microbiota homeostasis in obese mice.

This study explored the advantageous effects of purple sweet potato anthocyanin extract (PSPAE) on redox state in obese mice. The normal chow diet (NCD) group, high-fat/cholesterol diet (HCD) group, and three groups based on HCD and added with low, middle, and high dose of PSPAE (PAL, PAM, and PAH) were raised for 12 weeks. High dose of PSPAE treatment decreased the elevations of the body weight by 24.7%, serum total cholesterol by 48.3%, serum triglyceride by 42.4%, and elevated serum activities of glutathione peroxidase by 53.3%, superoxide dismutase by 57.8%, catalase by 75.4%, decreased serum contents of malondialdehyde by 27.1% and lipopolysaccharides by 40.5%, as well as increased caecal total short-chain fatty acid by 2.05-fold. Additionally, PSPAE depressed toll-like receptor 4 (TLR-4), nuclear factor kappa-B (NF-κB), interleukin 6, tumor necrosis factor α, and preserved nuclear factor erythroid-2-related factor 2 (Nrf2) gene expression. Similarly, the protein expression of Nrf2 was enhanced, while TLR-4 and p-NF-κB/NF-κB were depressed by PSPAE treatment. Moreover, PSPAE administration promoted the protection of intestinal barrier function and rebuilt gut microbiota homeostasis by blooming g_Akkermansia, g_Bifidobacterium, and g_Lactobacillus. Furthermore, antibiotic interference experiments showed that the gut microbiota was indispensable for preserving the redox state of PSPAE. These results suggested that PSPAE administration could be an opportunity for improving HCD-induced obesity and the redox state related to gut dysbiosis. PRACTICAL APPLICATION: Purple sweet potato anthocyanin has diverse pharmacological properties. It is applicable for individuals to consume extracts (as pills or other forms) from raw purple sweet potato if they want to improve obesity or redox state.

Engineering Extracellular Vesicles Enriched with Palmitoylated ACE2 as COVID-19 Therapy.

Angiotensin converting enzyme 2 (ACE2) is a key receptor present on cell surfaces that directly interacts with the viral spike (S) protein of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It is proposed that inhibiting this interaction can be promising in treating COVID-19. Here, the presence of ACE2 in extracellular vesicles (EVs) is reported and the EV-ACE2 levels are determined by protein palmitoylation. The Cys141 and Cys498 residues on ACE2 are S-palmitoylated by zinc finger DHHC-Type Palmitoyltransferase 3 (ZDHHC3) and de-palmitoylated by acyl protein thioesterase 1 (LYPLA1), which is critical for the membrane-targeting of ACE2 and their EV secretion. Importantly, by fusing the S-palmitoylation-dependent plasma membrane (PM) targeting sequence with ACE2, EVs enriched with ACE2 on their surface (referred to as PM-ACE2-EVs) are engineered. It is shown that PM-ACE2-EVs can bind to the SARS-CoV-2 S-RBD with high affinity and block its interaction with cell surface ACE2 in vitro. PM-ACE2-EVs show neutralization potency against pseudotyped and authentic SARS-CoV-2 in human ACE2 (hACE2) transgenic mice, efficiently block viral load of authentic SARS-CoV-2, and thus protect host against SARS-CoV-2-induced lung inflammation. The study provides an efficient engineering protocol for constructing a promising, novel biomaterial for application in prophylactic and therapeutic treatments against COVID-19.

Mild depolymerization of the sinocalamus oldhami alkali lignin to phenolic monomer with base and activated carbon supported nickel-tungsten carbide catalyst composite system.

In this study, the sinocalamus oldhami alkali lignin was depolymerized into phenolic products in a combined system by using the composite alkali and Ni-W2C/activated carbon (AC) as catalysts. FT-IR, GPC, TG, 2D-HSQC and GC-MS were used to analyze the composition, structure and distribution of degradation products, and the synergistic effect of metal and alkali catalysts on the depolymerization of lignin was also studied. The results showed that Ni-W2C/AC and composite alkali could effectively improve the catalytic degradation efficiency of lignin under mild conditions, 94.4% of lignin was converted and 17.18% of phenolic monomers were obtained under 260 °C for 5 h. In this composite system, the synergism of the basic sites, the metal active sites and the Lewis acid sites could promote the cleavage of C-O bonds in the lignin molecule and lower the char formation during the base-catalyzed solvolysis. Phenolic monomers were mainly composed of phenol, 2-methyl-phenol and p-cresol etc.

Dietary Supplementation of Apple Phlorizin Attenuates the Redox State Related to Gut Microbiota Homeostasis in C57BL/6J Mice Fed with a High-Fat Diet.

We explored the effects of dietary supplementation with phlorizin on redox state-related gut microbiota homeostasis in an obesity mouse model. Mice (C57BL/6J) were grouped as follows for 12 weeks: normal chow diet group (NCD), high-fat and cholesterol diet group (HFD), and treatment groups fed with HFD along with three levels of phlorizin. Phlorizin alleviated the hyperlipidemia and redox status and increased the total ccal SCFA content (1.88 ± 0.25 mg/g). Additionally, phlorizin regulated gene expression related to lipid metabolism, redox status, and cecum barrier and rebuilt gut microbiota homeostasis. After interference by antibiotics, the total phloretin content in the feces was decreased about 4-fold, and most of the health-promoting effects were abolished, indicating that phlorizin might be susceptible to microbial biotransformation and that microecology is indispensable for maintaining the redox state capacities of phlorizin. Phlorizin treatment could be an advantageous option for improving HFD-related obesity and redox states related to gut microbiota homeostasis.

Purple Sweet Potato Extract extends lifespan by activating autophagy pathway in male Drosophila melanogaster.

INTRODUCTION: Purple sweet potato is a nutritive food rich in anthocyanins that possess antioxidant effects. Drosophila melanogaster owns short growth cycle, fast reproduction, less chromosomes, more mutants, small individuals, therefore, which is an appropriate genetic model organism. OBJECTIVE: To investigate the anti-aging activity of Purple Sweet Potato Extract (PSPE) in male Drosophila melanogaster and explore the underlying mechanism. RESULTS: PSPE-induced longevity was associated with improvements in climbing ability and tolerance to stressors such as paraquat and hydrogen peroxide (H2O2). Furthermore, PSPE supplementation increased the activity of superoxide dismutase (SOD) and catalase (CAT), as well as expression of SOD and CAT genes, but decreased malondialdehyde (MDA) content. Meanwhile, PSPE decreased the intestinal stem cells (ISCs) proliferation and improved intestinal homeostasis, which was measured by Smurf assay and colony-forming units (CFUs) measurement in aging flies. Additionally, PSPE markedly inhibited the expression of upstream genes AKT-1, PI3K and mTOR and elevated the downstream gene 4E-BP, which further activated the expression of autophagy-related genes (Atg1, Atg5, Atg8a and Atg8b). Moreover, the production of lysosomes increased, indicating that the autophagy pathway was activated. CONCLUSION: The results provided direct evidence of PSPE anti-aging effects on an organism level, indicating PSPE could be developed for use in effective anti-aging products.

Ursolic acid alleviates lipid accumulation by activating the AMPK signaling pathway in vivo and in vitro.

The mechanism underlying the effect of ursolic acid (UA) on lipid metabolism remains unclear. This study aimed to explore the mechanisms of UA in reducing lipid accumulation in free fatty acids-cultured HepG2 cells and in high-fat-diet-fed C57BL/6J mice. In vivo, UA effectively alleviated liver steatosis and decreased the size of adipocytes in the epididymis. It also significantly decreased the total cholesterol (TC) and triglyceride (TG) contents in the liver and plasma in C57BL/6 mice. In vitro, UA (20 µM) significantly reduced lipid accumulation; the intracellular TC contents decreased from 0.078 ± 0.0047 to 0.049 ± 0.0064 µmol/mg protein, and TG contents from 0.133 ± 0.005 to 0.066 ± 0.0047 µmol/mg protein, in HepG2 cells. Furthermore, UA reduced the mRNA expression related to fat synthesis, enhanced the mRNA expression related to adipose decomposition, and dramatically upregulated the protein expression of P-AMPK in vivo and in vitro. Of note, these protective effects of UA on a high-fat environment were blocked by the AMPK inhibitor (compound C) in vitro. In addition, the molecular docking results suggested that UA could be docked to the AMPK protein as an AMPK activator. These results indicated that UA lowered the lipid content probably via activating the AMPK signaling pathway, thereby inhibiting lipid synthesis and promoting fat decomposition. PRACTICAL APPLICATION: Ursolic acid (UA) widely exists in vegetables and fruits. This study highlighted a lipid-lowing mechanism of UA in HepG2 cells and C57BL/6J mice. The data indicated that UA might be used in lipid-lowering functional foods.

Improved physicochemical stability of emulsions enriched in lutein by a combination of chlorogenic acid-whey protein isolate-dextran and vitamin E.

Lutein, as a bioactive substance, has the ability to decrease the risk of some chronic diseases, but the poor water solubility, chemical instability, and low bioaccessibility limit its wide application in foods. In this study, an emulsion-based delivery system stabilized by chlorogenic acid (CA)-whey protein isolate (WPI)-dextran (DEX) ternary conjugates was prepared and vitamin E (VE) was added to increase the chemical stability of lutein. Molecular weight and conformational information of ternary conjugates were obtained by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, fluorescence spectroscopy, and Fourier transform infrared spectroscopy. o-Phthalaldehyde results suggested that the extent of glycation was 16.4% and 19.5% for (CA-WPI)-DEX and WPI-DEX conjugates, respectively. The physicochemical stability of lutein-enriched emulsions was evaluated under different environmental stresses and long-term storage. The obtained results showed that compared with emulsions stabilized by WPI alone or binary conjugates, ternary conjugates imparted emulsions high stability under different environmental stress conditions (ionic strength, freeze-thaw, and heat) and long-term storage (within 3 weeks). VE can effectively decrease the degradation rate of lutein without changing the physical stability of emulsions. Additionally, the lutein-enriched emulsions prepared by ternary conjugates and VE exhibited a relatively high bioaccessibility. PRACTICAL APPLICATION: The ternary conjugates constructed in this paper has excellent physicochemical characteristics to stabilize emulsion, and can increase the water solubility of functional factors and reduce their degradation rate. Additionally, this conjugate was prepared by food-grade materials. Therefore, it can be used as emulsion-based delivery systems in food industrials.

Extracellular Vesicles in Cancer Immune Microenvironment and Cancer Immunotherapy.

Extracellular vesicles (EVs) are secreted by almost all cells. They contain proteins, lipids, and nucleic acids which are delivered from the parent cells to the recipient cells. Thereby, they function as mediators of intercellular communication and molecular transfer. Recent evidences suggest that exosomes, a small subset of EVs, are involved in numerous physiological and pathological processes and play essential roles in remodeling the tumor immune microenvironment even before the occurrence and metastasis of cancer. Exosomes derived from tumor cells and host cells mediate their mutual regulation locally or remotely, thereby determining the responsiveness of cancer therapies. As such, tumor-derived circulating exosomes are considered as noninvasive biomarkers for early detection and diagnosis of tumor. Exosome-based therapies are also emerging as cutting-edge and promising strategies that could be applied to suppress tumor progression or enhance anti-tumor immunity. Herein, the current understanding of exosomes and their key roles in modulating immune responses, as well as their potential therapeutic applications are outlined. The limitations of current studies are also presented and directions for future research are described.

The effect of collection substrate on electrospun ciprofloxacin-loaded poly(vinylpyrrolidone) and ethyl cellulose nanofibers as potential wound dressing materials.

In this work, nanofibers based on hydrophilic poly(vinylpyrrolidone) (PVP) and hydrophobic ethyl cellulose (EC) were generated via electrospinning. A model antibiotic, ciprofloxacin (CIF), was also incorporated into the fibers. Fibers were collected on both a foil substrate and a commercial gauze, the latter in the interests of developing a smart fabric. Electron microscopy images revealed that the fibers collected on both foil and fabric were homogeneous and cylindrical. Infrared spectroscopy, X-ray diffraction and differential scanning calorimetry demonstrated that CIF was successfully loaded into the fibers and present in the amorphous physical form. In vitro drug release tests were conducted to simulate drug release from the formulations into a wound site, and as expected the hydrophilic fibers showed much faster release than their hydrophobic analogues. CIF was released through a combined mechanism of polymer erosion and drug diffusion, and the EC nanofibers displayed close to zero-order release over three days. Fibroblast cells are able to grow and proliferate on the fibers. Finally, inhibition zone assays revealed that the growth of both Gram positive and Gram negative bacteria could be effectively inhibited as a result of the presence of CIF in the fibers. There were no marked differences between the fibers collected on foil and on gauze, and electrospinning can be performed directly onto a gauze substrate to prepare a smart fabric.

Electrospun oral formulations for combined photo-chemotherapy of colon cancer.

In this work, we report new formulations for the combined photo-chemotherapy of colon cancer. Fibers were fabricated via coaxial-electrospinning with the intent of targeting delivery of the anti-cancer drug carmofur (CAR) and the photosensitizer rose bengal (RB) selectively to the colon site. The fibers comprised a hydroxypropyl methylcellulose (HPMC) core loaded with the active ingredients, and a pH-sensitive Eudragit L100-55 shell. The fibers were found to be homogeneous and cylindrical and have visible core-shell structures. X-ray diffraction and differential scanning calorimetry demonstrated that both CAR and RB were present in the fibers in the amorphous physical form. In vitro drug release studies showed that the fibers have the potential to selectively deliver drugs to the colon, with only 10-15 % release noted in the acidic conditions of the stomach but sustained release at pH 7.4. Cytotoxicity studies were undertaken on human dermal fibroblast (HDF) and colon cancer (Caco-2) cells, and the influence of light on cell death was also explored. The fibers loaded with CAR alone showed obvious toxicity to both cell lines, with and without the application of light. The RB-loaded fibers led to high viability (ca. 80% for both cell types) in the absence of light, but much greater toxicity was noted (30-50%) with light. The same trends were observed with the formulation containing both CAR and RB, but with lower viabilities. The RB and RB/CAR loaded systems show clear selectivity for cancerous over non-cancerous cells. Finally, mucoadhesion studies revealed there were strong adhesive forces between the rat colonic mucosa and the fibers after they had passed through an acidic environment. Such electrospun fibers thus could have potential in the development of oral therapies for colon cancer.

Interleukin-1ß-induced IRAK1 ubiquitination is required for TH-GM-CSF cell differentiation in T cell-mediated inflammation.

Accumulating evidence suggests granulocyte macrophage-colony stimulating factor (GM-CSF) can function as an inflammatory mediator, but whether GM-CSF-producing CD4+ T cells (TH-GM-CSF) are a distinct T helper cell subset is lacking. Herein we demonstrate that interleukin (IL)-1ß exclusively drives differentiation of naïve CD4+ T cells into TH-GM-CSF cells via inducing ubiquitination of IL-1 receptor-associated kinase 1 (IRAK1) and subsequent activation of the transcription factor NF-kappaB (NF-κB), independent of RAR-related orphan receptor gamma (RORγt) required for TH17 differentiation. In vivo, TH-GM-CSF cells are present in murine Citrobacter Rodentium infections and mediate colitis following adoptive transfer of CD4+ T cells into Rag1-/- mice via GM-CSF-induced macrophage activation. The TH-GM-CSF cell phenotype is stable and distinct from the TH17 genetic program, but IL-1ß can convert pre-formed TH17 cells into TH-GM-CSF cells, thereby accounting for previously reported associations between IL-17 and GM-CSF. Together, our results newly identify IL-1ß/NF-κB-dependent TH-GM-CSF cells as a unique T helper cell subset and highlight the importance of CD4+ T cell-derived GM-CSF induced macrophage activation as a previously undescribed T cell effector mechanism.