Search

Overexpression of T‐cell immunoglobulin and mucin‐domain containing‐3 (TIM‐3) on T cells has been observed in smokers. However, whether and how galectin‐9 (Gal‐9)/TIM‐3 signal between T‐regulatory cells (Tregs) and type 17 helper (Th17) cells contributes to tobacco smoke‐induced airway inflammation remains unclear. Here, we aimed to explore the role of the Gal‐9/TIM‐3 signal between Tregs and Th17 cells during chronic tobacco smoke exposure. Tregs phenotype and the expression of TIM‐3 on CD4+ T cells were detected in a mouse model of experimental emphysema. The role of TIM‐3 in CD4+ T cells was explored in a HAVCR2−/− mouse model and in mice that received recombinant anti‐TIM3. The crosstalk between Gal‐9 and Tim‐3 was evaluated by coculture Tregs with effector CD4+ T cells. We also invested the expression of Gal‐9 in Tregs in patients with COPD. Our study revealed that chronic tobacco smoke exposure significantly reduces the frequency of Tregs in the lungs of mice and remarkably shapes the heterogeneity of Tregs by downregulating the expression of Gal‐9. We observed a pro‐inflammatory but restrained phenotypic transition of CD4+ T cells after tobacco smoke exposure, which was maintained by TIM‐3. The restrained phenotype of CD4+ T cells was perturbed when TIM‐3 was deleted or neutralised. Tregs from the lungs of mice with emphysema displayed a blunt ability to inhibit the differentiation and proliferation of Th17 cells. The inhibitory function of Tregs was partially restored by using recombinant Gal‐9. The interaction between Gal‐9 and TIM‐3 inhibits the differentiation of Th17 cells and promotes apoptosis of CD4+ T cells, possibly by interfering with the expression of retinoic acid receptor‐related orphan receptor gamma t. The expression of Gal‐9 in Tregs was reduced in patients with COPD, which was associated with Th17 response and lung function. These findings present a new paradigm that impairment of Gal‐9/Tim‐3 crosstalk between Tregs and Th17 cells during chronic tobacco smoke exposure promotes tobacco smoke‐induced airway/lung inflammation. [ABSTRACT FROM AUTHOR]

Anti-interferon-γ autoantibodies (AIGAs) syndrome is susceptible to disseminated opportunistic infections due to increased AIGAs, but its clinical immunological characteristics remain unrecognized. We conducted a prospective cohort study between January 2021 and December 2023, recruiting patients with opportunistic infections who were categorized into AIGAs-positive and AIGAs-negative groups. Clinical immunological data and outcomes were documented. A subset of AIGAs-positive patients received glucocorticoid treatment, and its effectiveness was evaluated. A total of 238 patients were enrolled, with 135 AIGAs-positive and 103 AIGAs-negative patients. AIGAs-positive patients showed higher rates of multiple pathogen dissemination, shorter progression-free survival (PFS), and increased exacerbation frequency. They also showed elevated erythrocyte sedimentation rate (ESR), globulin (GLB), immunoglobulin (Ig)G, IgE, and IgG4 levels. Among the 70 AIGAs-positive patients monitored for at least six months, three subtypes were identified: high AIGAs titer with immune damage, high AIGAs titer without immune damage, and low AIGAs titer without immune damage. Of the 55 patients followed for 1 year, decreasing AIGAs titer and immune indices (GLB, IgG, IgE, IgG4) were observed. Among the 31 patients with high AIGAs titer and immune damage treated with low-dose glucocorticoids at the stable phase, reductions were observed in immune indices and AIGAs titer in 67.74% of cases. In summary, AIGAs-positive patients exhibit infectious and immunological characteristics. Elevated AIGAs, IgG, IgG4, and IgE indicate abnormal immune damages. AIGAs titer generally decrease over time. Stable-phase AIGAs-positive patients can be categorized into three subtypes, with those having high AIGAs titer and increased immune indices potentially benefitting from glucocorticoid treatment.

The involvement of Group 3 innate lymphoid cells (ILC3s) and dendritic cells (DCs) in chronic lung inflammation has been increasingly regarded as the key to understand the inflammatory mechanisms of smoke-related chronic obstructive pulmonary disease (COPD). However, the mechanism underlying the engagement of both remains unclear. Our study aimed to explore NCR - ILC3 differentiation in the lungs of mice exposed to cigarette smoke (CS) and to further investigate whether DCs activated by CS exposure contribute to the differentiation of ILCs into NCR - ILC3s. The study involved both in vivo and in vitro experiments. In the former, the frequencies of lung NCR - ILC3s and NKp46 - IL-17A + ILCs and the expression of DCs, CD40, CD86, IL-23, and IL-1β quantified by flow cytometry were compared between CS-exposed mice and air-exposed mice. In the latter, NKp46 - IL-17A + ILC frequencies quantified by flow cytometry were compared after two cocultures, one involving lung CD45 + Lin - CD127 + ILCs sorted from air-exposed mice and DCs sifted by CD11c magnetic beads from CS-exposed mice and another including identical CD45 + Lin - CD127 + ILCs and DCs from air-exposed mice. The results indicated significant increases in the frequencies of NCR - ILC3s and NKp46 - IL-17A + ILCs; in the expression of DCs, CD40, CD86, IL-23, and IL-1β in CS-exposed mice; and in the frequency of NKp46 - IL-17A + ILCs after the coculture with DCs from CS-exposed mice. In conclusion, CS exposure increases the frequency of lung ILCs and NCR - ILC3s. CS-induced DC activation enhances the differentiation of ILCs into NCR - ILC3s, which likely acts as a mediating step in the involvement of NCR-ILC3s in chronic lung inflammation.

Background: The precise function of Tolloid Like 2 (TLL2) remains uncertain within the context of Lung Adenocarcinoma (LUAD)., Objective: The primary objective of this investigation was to conduct a thorough analysis., Methods: To assess its diagnostic utility, data from The Cancer Genome Atlas (TCGA) database were used to assess TLL2 expression in pan-cancer and LUAD. The study has also investigated the correlation between TLL2 expression levels and LUAD symptoms and prognosis. Furthermore, the study has explored possible regulatory networks involving TLL2, including its association with immune infiltration, tumor stemness index (mRNAsi), and drug sensitivity in LUAD. We have explored TLL2 expression in single-cell sequencing of LUAD and the genomic variation and clinical significance of TLL2 in LUAD. The expression of TLL2 has been validated in GSE87340 and cell lines by quantitative Real-time PCR (qRT-PCR)., Results: An abnormal expression of TLL2 has been found in pan-cancer and LUAD. In LUAD patients, elevated levels of TLL2 were significantly related to the T stage (p = 0.046) and the pathological stage (p = 0.016). The expression of TLL2 in patients with LUAD was significantly associated with poorer Overall Survival (OS) (p < 0.001). The expression of TLL2 was determined to be an independent predictor of poorer OS (p = 0.042). TLL2 was associated with ribosome, neuroactive ligand-receptor interaction, allograft rejection, ECM receptor interaction, asthma, porphyrin and chlorophyll metabolism, focal adhesion, pentose and glucuronate inter-conversions, and ascorbate and aldarate metabolism. The expression of TLL2 in LUAD was correlated with immune infiltration and mRNAsi. The expression of TLL2 was significantly and negatively correlated with TAK-715, XMD13-2, STF-62247, OSI-930, and EHT-1864 in LUAD. The TLL2 gene was up- -regulated in multiple individual LUAD cells. LUAD patients with altered TLL2 had a shorter PFS as opposed to those with unaltered TLL2. The expression of TLL2 was significantly increased in LUAD cells., Conclusion: For patients with LUAD, TLL2 may serve as an immunotherapeutic target and a useful prognosis biomarker., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Amino acid homeostasis is interconnected with the immune network of plants. During plant-pathogen interaction, amino acid transporters (AATs) have been shown to be involved in plant immune responses. However, the molecular mechanism by which how AATs function in this process remains elusive. In this study, we identify OsMP1 that acts as a quantitative trait locus against blast fungus from a joint analysis of GWAS and QTL mapping in rice. Heterogeneous expression of OsMP1 in yeast supports its function in transporting a wide range of amino acids, including Thr, Ser, Phe, His and Glu. OsMP1 could also mediate 15N-Glu efflux and influx in Xenopus oocyte cells. The expression of OsMP1 is dramatically induced by Magnaporthe oryzae in the resistant landrace Heikezijing, while remaining unresponsive in the susceptible landrace Suyunuo. Overexpressing OsMP1 in Suyunuo enhances disease resistance to blast fungus and leaf-blight bacterium without yield penalty. Furthermore, the overexpression of OsMP1 leads to increased accumulation of Thr, Ser, Phe and His in the leaves. And the heightened levels of these amino acids contribute to reduced disease susceptibility, which is associated with upregulated jasmonic acid pathway. Thus, our results elucidate the pivotal role of OsMP1 in disease resistance and provide a potential target for breeding more resistant rice cultivars without compromising yield., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background and Objective: Recent studies have shown that integrin α5β1 as a core in the integrin family plays an important role in metastasis, invasion and poor difference of non-small cell lung cancer. In this study, A549 cells were cultured and treated with integrin α5β1 small interfering RNA (siRNA) and extracelluar signal-regulated protein kinase (ERK) inhibitor PD98059 to investigate the effect of integrin α5β1 on proliferation and migration of A549 cells and explore its signal transduction mechanism., Methods: A549 cells were divided into four groups: Untransfection, Lipofectamine, Integrin α5β1 siRNA-transfected group and PD98059 group. The protein expression levels of integrin α5β1 were detected by Western blot analysis and the expression levels of integrin α5β1 mRNA was measured by reverse transcription-polymerase chain reaction (RT-PCR). The protein expression level of ERK1/2, MMP-9 and caspase-3 were measured by Western blot analysis. The proliferation and apoptosis of A549 cells were measured by MTT assay and Annexin-V FITC PI double staining., Results: Integrin α5β1 siRNA could inhibit the phosphorylated ratio of ERK by down-regulate the expression of ERK 1/2 proteins. In addition, integrin α5β1 siRNA or PD98059 could inhibit the proliferation of A549 cells, induce the apoptosis of A549 cells, up-regulate the expression of caspase-3 and down-regulate the expression of MMP-9., Conclusions: Integrin α5β1 might involves the abnormal proliferation and migration of A549 cells through mediating ERK signal transduction pathway.