BACKGROUND: We investigated the function of type 2 innate lymphoid cells (ILC2s) and IL-33 in pulmonary tuberculosis (PTB).
METHODS: Peripheral blood samples were collected from PTB patients and healthy controls. The cytometric bead array was used to detect plasma IL-33, TGF-β, IL-4, IL-5, IL-6, IL-10, IL-13, and soluble ST2 (sST2). ILC2s, Th2, and Treg cells were detected with flow cytometry. Quantitative real-time PCR was used to measure mRNA levels. ILC2s were co-cultured with peripheral blood mononuclear cells and then intervened with IL-33 or anti-ST2 antibody + IL-33 in vitro. IL-4, IL-6, IL-5, IL-10, IL-13, and TGF-β levels were measured by enzyme-linked immunosorbent assay.
RESULTS: Compared with healthy controls, the levels of IL-33, sST2, TGF-β, IL-10, and IL-6 in the plasma of PTB patients were significantly higher. No significant difference was found in the plasma IL-4, IL-5, and IL-13 levels. Patients with PTB had significantly increased ILC2s proportion and mRNA levels of RAR-related orphan receptor α and GATA binding protein 3. After 48 h of IL-33 stimulation in vitro, Treg cell proportion significantly increased and the IL-10 level was significantly elevated. Treatment with anti-ST2 abolished these effects. No significant difference was found in cytokines of IL-4, IL-6, IL-5, IL-13, and TGF-β, or Th2 cells before and after IL-33 treatment. ILC2s proportion in peripheral blood was increased and plasma IL-33 was upregulated in PTB patients.
CONCLUSIONS: IL-33 may promote the growth of ILC2s and the production of Treg-related cell cytokines, but not Th2-related cell cytokines, to participate in immune response to PTB.

Objective To investigate the effects of astragaloside IV(AS-IV) on the balance of T helper type 1 (Th1) and Th2 cells in mice with IgA nephropathy (IgAN) and its possible mechanism. Methods The IgAN model of BALB/c mice was established. Successfully modeled mice were randomly divided into four groups: model, AS-IV low dose, AS-IV medium dose and AS-IV high dose groups, with 10 mice in each group. Another 10 mice served as the control group. Mice in the low, medium and high dose groups were administered 12.5, 25 and 50 mg/kg AS-IV suspension (prepared in normal saline) by gavage, while the control and model groups were given an equivalent volume of normal saline. The 24-hour urinary protein (24 h UPr) content and urine red blood cell count were measured in each group. The levels of blood urea nitrogen (BUN), serum creatinine (Scr) and albumin (ALB) were determined. Serum interferon γ (IFN-γ), interleukin 4 (IL-4) and IL-10 levels were detected by ELISA. The ratio of Th1/Th2 cells in peripheral blood of mice was detected using flow cytometry. Histopathological changes in the kidney of mice were observed by HE staining. RT-PCR and Western blot were used to detect the mRNA and protein expressions of T cell immunoglobulin and mucin domain gene 1 (TIM-1), Toll-like receptor 4 (TLR4) in mouse kidney tissue. Results Compared with the model group, in weeks 12 and 15, the urine red blood cell count, 24 h UPr, BUN, Scr, levels of IL-4 and IL-10, the proportion of Th2 cells, as well as the mRNA and protein expression levels of TIM-1 and TLR4 were significantly decreased in the low, medium and high dose groups of AS-IV, and the levels of ALB, IFN-γ, the proportion of Th1 cells and Th1/Th2 cell ratio were increased, with the high-dose group showing the best effects. Conclusion AS-IV can inhibit TIM-1 signaling pathway, increase the Th1/Th2 cell ratio, inhibit the inflammatory reaction, and alleviate the renal injury in IgAN mice.

Although various anti-inflammatory medications, such as ephedrine, are employed to manage cough-variant asthma, their underlying mechanisms are yet to be fully understood. Recent studies suggest that exosomes derived from airway epithelial cells (AECs) contain components like messenger RNAs (mRNAs), micro-RNAs (miRNAs), and long noncoding RNA (lncRNA), which play roles in the occurrence and progression of airway inflammation. This study investigates the influence of AEC-derived exosomes on the efficacy of ephedrine in treating cough-variant asthma. We established a mouse model of asthma and measured airway resistance and serum inflammatory cell levels. Real-time polymerase chain reaction (RT-qPCR), Western blotting, and enzyme-linked immunosorbent assay (ELISA) analyses were used to assess gene and protein expression levels. Exosomes were isolated and characterized. RNA immunoprecipitation (RIP) and RNA pull-down assays were conducted to examine the interaction between hnRNPA2B1 and lnc-TRPM2-AS1. In the ovalbumin (OVA)-challenged mouse model, ephedrine treatment reduced inflammatory responses, airway resistance, and Th1/Th2 cell imbalance. Exosomes from OVA-treated AECs showed elevated levels of lnc-TRPM2-AS1, which were diminished following ephedrine treatment. The exosomal lnc-TRPM2-AS1 mediated the Th1/Th2 imbalance in CD4+ T cells, with its packaging into exosomes being facilitated by hnRNPA2B1. This study unveils a novel mechanism by which ephedrine ameliorates OVA-induced CD4+ T cell imbalance by suppressing AEC-derived exosomal lnc-TRPM2-AS1. These findings could provide a theoretical framework for using ephedrine in asthma treatment.

Shen chan decoction (SCD) as a significant Traditional Chinese medicine (TCM) to treat atopic dermatitis (AD), but its mechanism of action has not been clarified, so we started the present study, first possible effects of SCD on AD were predicted using network pharmacology. Next, dinitrochlorobenzene was used to establish a mouse model of AD. After successful modelling, the SCD were administered intragastrically to treat the mice. Eventually, the KEGG pathway enrichment analysis indicated that SCD improved AD mainly through effects on inflammation and the gut microbiota. The experimental findings revealed that SCD treatment attenuated AD symptoms and downregulate the characteristic immune factors, namely IL-4, IL-6 and IgE. Moreover, it promoted a balance between Th1/Th2 cells. Furthermore, the itch signaling pathways involving H1R/PAR-2/TRPV1 were inhibited. The 16S rRNA sequencing results indicated that SCD administration influenced the Firmicutes/Bacteroidetes ratio at the phylum level by augmenting the relative proportions of Lactobacillaceae and Muribaculaceae at the family and genus levels, while decreasing the abundances of Lactococcus and Ruminococcus. These findings suggest that internal administration of SCD is an effective therapeutic approach for AD. We suggest that SCD may be an alternative therapy for the treatment of AD.Additionally, it could offer valuable insights into the pathogenesis of AD and the development of innovative therapeutic agents.

Recent evidence has shown that T cell exhaustion is implicated in Allergen-specific Immunotherapy (AIT). However, how T cell exhaustion plays a role in AIT is far from clear. Our study aimed to investigate T cell exhaustion associated with allergen exposure during AIT in mice. Ovalbumin (OVA) - sensitized C57BL/6J asthma mouse and AIT mouse models were constructed. Quantitative real-time PCR (qRTPCR) and flow cytometry were used to monitor the occurrence of local and systemic CD4+ T cells and Th2+T cells exhaustion in OVA-sensitized mice. The inhibitory surface marker programmed cell death protein 1 (PD-1) on CD4+ T cells and Th2+T cells was significantly upregulated in AIT mice compared with asthmatic and control mice. The level of PD-1 on the surface of CD4+T cells of asthma mice was significantly higher than that of control mice. The inhibitory surface marker cytotoxic T lymphocyte-associated protein 4 (CTLA-4) on CD4+ T cells and Th2+T cells showed no significant difference between the AIT, asthma and control mice. Collectively, our study indicated that the expression of PD-1 on CD4+ T cells and Th2+T cells was increased in AIT. Allergen exposure promotes the expression of PD-1 on the surface of CD4+ T cells. T cell exhaustion plays an important role in AIT.

Type 2 innate lymphoid cells (ILC2) initiate early allergic inflammation in the lung, but the factors that promote subsequent resolution of type 2 inflammation and prevent prolonged ILC2 activation are not fully known. Here we show that SLAM-family receptors (SFR) play essential roles in this process. We demonstrate dynamic expression of several SFRs on ILC2s during papain-induced type 2 immunity in mice. SFR deficiency exacerbates ILC2-driven eosinophil infiltration in the lung, and results in a significant increase in IL-13 production by ILC2s exclusively in mediastinal lymph nodes (MLN), leading to increased dendritic cell (DC) and TH2 cell numbers. In MLNs, we observe more frequent interaction between ILC2s and bystander T cells, with T cell-expressed SFRs (especially SLAMF3 and SLAMF5) acting as self-ligands to suppress IL-13 production by ILC2s. Mechanistically, homotypic engagement of SFRs at the interface between ILC2s and T cells delivers inhibitory signaling primarily mediated by SHIP-1. This prevents activation of NF-κB, driven by IL-7 and IL-33, two major drivers of ILC2-mediated type 2 immunity. Thus, our study shows that an ILC2-DC-TH2 regulatory axis may promote the resolution of pulmonary type 2 immune responses, and highlights SLAMF3/SLAMF5 as potential therapeutic targets for ameliorating type 2 immunity.

BACKGROUND: Allergic rhinitis (AR) is an allergic disease characterized by the dominant differentiation of T helper cell 2 (Th2). BACH2 plays a key role in regulating Th2 immune response. This study aimed to explore the association between BACH2 single nucleotide polymorphism (SNPs) and susceptibility to AR.
METHODS: Han population from northern Shaanxi, China was chosen as subjects. After the DNA extraction from the peripheral blood of subjects, genotyping was completed through the Agena MassARRAY platform. Logistic regression analysis was used to assess the association. Multivariate dimensionality reduction (MDR) was used to evaluate the effect of the interaction between \'SNP-SNP\' on susceptibility to AR. Using false-positive report probability (FPRP) analysis to test whether the significant results obtained in this study were noteworthy.
RESULTS: BACH2-rs905670 and -rs2134814 were significantly associated with increased risk of AR. The mutant allele \'A\' of rs905670 (OR = 1.36, p = 0.018) and mutant allele \'G\' of rs2134814 (OR = 1.34, p = 0.027) were risk genetic factors for AR. The above genetic association was further observed in the stratified analysis: BACH2-rs905670 and-rs2134814 were significantly associated with an increased risk of AR in females, aging older than 43 years, and participants working and living in the loess hills (OR > 1, p < 0.05).
CONCLUSIONS: BACH2-rs905670 and -rs2134814 are significantly associated with increasing AR risk.

Scy p 8 (triosephosphate isomerase) as a crab allergen in inducing distinct T-helper (Th) cell differentiation and a linear epitope associated with allergenicity remain elusive. In this study, mice sensitized with Scy p 8 exhibited significantly upregulated levels of IgE, IgG1, and IL-4 release, inducing a Th2 immune response. Moreover, the release of IFN-γ (Th1) and the levels of Treg cells were downregulated, while IL-17A (Th17) was upregulated, indicating that Scy p 8 disrupted the Th1/Th2 balance and Th17/Treg balance in mice. Furthermore, bioinformatics prediction and serum samples from crab-allergic patients and mice enabled the discovery of 8 linear epitopes of Scy p 8. Meanwhile, the analysis of peptide similarity and tertiary superposition revealed that 8 epitopes of Scy p 8 exhibited conservation across various species, potentially resulting in cross-reactivity. These findings possess the potential to enhance the comprehension of crab allergens, thereby establishing a foundation for investigating cross-reactivity.

Allergic rhinitis (AR), a common disease in otolaryngology, is a key risk factor for poorly controlled asthma and many complications, although it is not life-threatening. The negative impact of AR on social productive forces and human health is no less than that of asthma. Dendritic cells (DCs) play an important role in AR. In addition to sharing some of DC\'s biological characteristics, DCs-derived exosomes (DEXs) can promote the priming and activation of T cells and the maturation and differentiation of T helper type 2 (Th2) cells. Multiple signaling pathways in AR can be modulated by DEXs, which present allergens and participate in allergic immune responses. Anti-allergic drugs can be carried by DEXs to alleviate allergic airway inflammation and treat Th2-mediated AR effectively. Therefore, DEXs are crucial in the pathogenesis and treatment of AR.

Tropomyosin has been identified as the major cross-reactive shellfish allergen, but recent studies showed the presence of other clinically relevant allergens. This study aims at determining the allergic immune responses of mice sensitized with raw and boiled shrimp extracts in comparison to recombinant tropomyosin (rTM). Female Balb/c mice were intragastrically sensitized and challenged with raw, boiled shrimp or rTM. Systemic, cellular and humoral allergic responses were compared, while allergenicity of the extracts was also compared by skin prick test (SPT) and immunoblot on shrimp allergic subjects. We showed that rTM and shrimp extracts induced IgE- and Th2-mediated allergic responses in mice, distinguished by remarkable intestinal inflammation in small intestine across all regimens. Notably, boiled shrimp extract exhibited the highest sensitization rate (73.7% of mice developed positive TM-specific IgE response) when compared with raw extract (47.8%) and rTM (34.8%). Mice sensitized with boiled extract manifested the highest allergen-specific IgE and Th2 cytokine responses than the others. Immunoblot results indicated that tropomyosin remained the major allergen in extract-based sensitization and had stronger allergenicity in a heat-treated form comparing to untreated TM, which was in line with the SPT results that boiled extract induced larger wheal size in patients. Hemocyanin and glycogen phosphorylase were also identified as minor allergens associated with manifestation of shrimp allergy. This study shows that boiled extract enhanced sensitization and Th2 responses in agreement with the higher allergenicity of heat-treated TM. This study thus presents three shrimp allergy murine models suitable for mechanistic and intervention studies, and in vivo evidence implies higher effectiveness of boiled extract for the clinical diagnosis of shellfish allergy.