Immunology最新文献

Maintaining intracellular redox balance is essential for the survival, antibody secretion, and mucosal immune homeostasis of immunoglobulin A (IgA) antibody-secreting cells (ASCs). However, the relationship between mitochondrial metabolic enzymes and the redox balance in ASCs has yet to be comprehensively studied. Our study unveils the pivotal role of mitochondrial enzyme PCK2 in regulating ASCs' redox balance and intestinal homeostasis. We discover that PCK2 loss, whether globally or in B cells, exacerbates dextran sodium sulphate (DSS)-induced colitis due to increased IgA ASC cell death and diminished antibody production. Mechanistically, the absence of PCK2 diverts glutamine into the TCA cycle, leading to heightened TCA flux and excessive mitochondrial reactive oxygen species (mtROS) production. In addition, PCK2 loss reduces glutamine availability for glutathione (GSH) synthesis, resulting in a decrease of total glutathione level. The elevated mtROS and reduced GSH expose ASCs to overwhelming oxidative stress, culminating in cell apoptosis. Crucially, we found that the mitochondria-targeted antioxidant Mitoquinone (Mito-Q) can mitigate the detrimental effects of PCK2 deficiency in IgA ASCs, thereby alleviating colitis in mice. Our findings highlight PCK2 as a key player in IgA ASC survival and provide a potential new target for colitis treatment.

Intermittent fasting (IF) refers to periodic fasting routines, that caloric intake is minimized not by meal portion size reduction but by intermittently eliminating ingestion of one or several consecutive meals. IF can instigate comprehensive and multifaceted alterations in energy metabolism, these metabolic channels may aboundingly function as primordial mechanisms that interface with the immune system, instigating intricate immune transformations. This review delivers a comprehensive understanding of IF, paying particular attention to its influence on the immune system, thus seeking to bridge these two research domains. We explore how IF effects lipid metabolism, hormonal levels, circadian rhythm, autophagy, oxidative stress, gut microbiota, and intestinal barrier integrity, and conjecture about the mechanisms orchestrating the intersect between these factors and the immune system. Moreover, the review includes research findings on the implications of IF on the immune system and patients burdened with autoimmune diseases.

Liu X, Xu X, Liao Y, Yao W, Geng X, Zeng X, et al. Psychological stress to ovalbumin peptide-specific T-cell receptor transgenic mice impairs the suppressive ability of type 1 regulatory T cell. Immunology. 2024;172(2):210–25. https://doi.org/10.1111/imm.13767.

Authors checked the data of the paper recently and found that Figure 2b is unnecessary. While the old Figure 2b describes a portion of the same data, which are described in Figure 2a. It is unnecessary to repeatedly present these data. Thus, authors removed the old Figure 2b from fig. 1._

We apologise for this error.

The explicit identification of CD8⁺ T cell subpopulation is important for deciphering the role of CD8⁺ T cells for protecting our body against invading pathogens and cancer. Our generated monoclonal antibody (mAb), named FE-1H10, recognized two novel subpopulations of peripheral blood CD8⁺ T cells, FE-1H10⁺ and FE-1H10⁻ CD8⁺ T cells. The molecule recognized by mAb FE-1H10 (FE-1H10 molecules) had a higher distribution on effector memory CD8⁺ T cell subsets. The functions of FE-1H10⁻ and FE-1H10⁺ CD8⁺ T cells were investigated. T cell proliferation assays revealed that FE-1H10⁻ CD8⁺ T cells exhibited a higher proliferation rate than FE-1H10⁺ CD8⁺ T cells, whereas FE-1H10⁺ CD8⁺ T cells produced higher levels of IFN-γ and TNF-α than FE-1H10⁻ CD8⁺ T cells. In T cell cytotoxicity assays, FE-1H10⁺ CD8⁺ T cells were able to kill target cells better than FE-1H10⁻ CD8⁺ T cells. RNA-sequencing analysis confirmed that these subpopulations were distinct: FE-1H10⁺ CD8⁺ T cells have higher expression of genes involved in effector functions (IFNG, TNF, GZMB, PRF1, GNLY, FASL, CX3CR1) while FE-1H10⁻ CD8⁺ T cells have greater expression of genes related to memory CD8⁺ T cell populations (CCR7, SELL, TCF7, CD40LG). The results suggested that mAb FE-1H10 identifies two novel distinctive CD8⁺ T cell subpopulations. The FE-1H10⁺ CD8⁺ T cells carried a superior functionality in response to tumour cells. The uncover of these novel CD8⁺ T cell subpopulations may be the basis knowledge of an optional immunotherapy for the selection of potential CD8⁺ T cells in cancer treatment.

Expansion of CD4⁺CD28^null T-lymphocytes is common in chronic heart failure (CHF) patients. Its ability to produce high levels of proinflammatory cytokines is probably the key role of these cells in CHF. IL-10 is a candidate for limiting CD4⁺CD28^null T-lymphocyte responses, whereas tumour necrosis factor (TNF) is the cytokine most closely involved in the loss of CD28 expression. Serum levels of TNF and IL-10 were measured in 65 CHF patients (mean age, 65.2 ± 13.84 years). Patients with an IL-10/TNF ratio ≥1 had significantly lower levels of CD4⁺CD28^null T-lymphocytes than those with a ratio <1. In vitro, IL-10 reduced the frequency of proliferative CD4⁺CD28^null T-lymphocytes stimulated with anti-CD3. Pre-treatment with IL-10 before anti-CD3 stimulation was required for the cytokine to inhibit TNF production by CD4⁺CD28^null T-lymphocytes. In addition to the previously described effect of IL-10 on HLA-DR and ICAM-1 expression, LFA-3 protein and mRNA levels were reduced in the presence of the cytokine in monocytes. IL-10 inhibition on CD4⁺CD28^null T-lymphocytes may be mediated by a reduction in HLA class II and LFA-3 expression because blocking interactions with these costimulators has similar effects to those of IL-10 treatment. Moreover, costimulation through CD2/LFA-3 interaction is enough to induce proliferation and cytokine production in CD4⁺CD28^null T-lymphocytes.

Tuberculosis (TB) alone caused over a billion deaths in the last 200 years, making it one of the deadliest diseases to humankind. Understanding the immune mechanisms underlying protection or pathology in TB is key to uncover the much needed innovative approaches to tackle TB. The scavenger receptor cysteine-rich molecule CD5 antigen-like (CD5L) has been associated with TB, but whether and how CD5L shapes the immune response during the course of disease remains poorly understood. Here, we show an upregulation of CD5L in circulation and at the site of infection in C57BL/6 Mycobacterium tuberculosis-infected mice. To investigate the role of CD5L in TB, we studied the progression of M. tuberculosis aerosol infection in a recently described genetically engineered mouse model lacking CD5L. Despite the increase of CD5L during infection of wild-type mice, absence of CD5L did not impact bacterial burden, histopathology or survival of infected mice. Absence of CD5L associated with a modest increase in the numbers of CD4+ T cells and the expression of IFN-γ in the lungs of infected mice, with no major effect in overall immune cell dynamics. Collectively, this study confirms CD5L as a potential diagnostic biomarker to TB, showing no discernible impact on the outcome of the infection.

The activation of CD4+ T-cells in a T cell receptor (TCR)-dependent antigen-specific manner is a central characteristic of the adaptive immune response. In addition to ensuring that CD4+ T-cells recognise their cognate antigen during activation, TCR-mediated signalling can also direct the outcome of differentiation. In both in vivo and in vitro model systems, strong TCR signalling has been demonstrated to drive Th1 differentiation, whereas weak TCR signalling drives Th2 responses. During the process of differentiation, TCR signal strength acts as a quantitative component in combination with the qualitative effects imparted by cytokines to polarise distinct T-helper lineages. Here, we investigated the role of interleukin 2 (IL-2) signalling in determining the outcome of TCR-dependent differentiation. IL-2 production was initiated as an early response to TCR-induced activation and was regulated by the strength of TCR signalling initially received. In the absence of IL-2, TCR dependent differentiation was found to be abolished. However, proliferative responses and early markers of activation were maintained, including the upregulation of GATA3, Tbet and Foxp3 at 24 h post-stimulation. Demonstrating that IL-2 signalling has a key role in stabilising and amplifying lineage-specific transcirption factor expression during differentiation. Further, activation of IL-2-deficient T-cells in the presence of exogenous cytokines was sufficient to restore differentiation whilst maintaining transcriptional signatures imparted during initial TCR signalling. Combined, our data demonstrate that the integration of quantitative TCR-dependent signalling and qualitative IL-2 signalling is essential for determining the fate of CD4+ T-cells during differentiation.

The cross-regulation of immunity and metabolism is currently a research hotspot in life sciences and immunology. Metabolic immunology plays an important role in cutting-edge fields such as metabolic regulatory mechanisms in immune cell development and function, and metabolic targets and immune-related disease pathways. Protein post-translational modification (PTM) is a key epigenetic mechanism that regulates various biological processes and highlights metabolite functions. Currently, more than 400 PTM types have been identified to affect the functions of several proteins. Among these, metabolic PTMs, particularly various newly identified histone or non-histone acylation modifications, can effectively regulate various functions, processes and diseases of the immune system, as well as immune-related diseases. Thus, drugs aimed at targeted acylation modification can have substantial therapeutic potential in regulating immunity, indicating a new direction for further clinical translational research. This review summarises the characteristics and functions of seven novel lysine acylation modifications, including succinylation, S-palmitoylation, lactylation, crotonylation, 2-hydroxyisobutyrylation, β-hydroxybutyrylation and malonylation, and their association with immunity, thereby providing valuable references for the diagnosis and treatment of immune disorders associated with new acylation modifications.

SET domain-containing 2 (SETD2) is a histone methyltransferase. It regulates the activity of H3K36me3 to enhance gene transcription. Macrophages (Mϕs) are one of the cell types involved in immune response. The purpose of this study is to clarify the role of SETD2 in regulating the immune property of Mϕ. The Mφs were isolated from the bronchoalveolar lavage fluid (BALF) and analysed through flow cytometry and RNA sequencing. A mouse strain carrying Mφs deficient in SETD2 was used. A mouse model of airway allergy was established with the ovalbumin/alum protocol. Less expression of SETD2 was observed in airway Mϕs in patients with allergic asthma. SETD2 of M2 cells was associated with the asthmatic clinical response. Sensitization reduced the expression of SETD2 in mouse respiratory tract M2 cells, which is associated with the allergic reaction. Depletion of SETD2 in Mφs resulted in Th2 pattern inflammation in the lungs. SETD2 maintained the immune regulatory ability in airway M2 cells. SETD2 plays an important role in the maintenance of immune regulatory property of airway Mφs.

Lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer, and the early detection and diagnosis of this disease are crucial in reducing mortality rates. The timely diagnosis of LUAD is essential for controlling tumour development and enabling early surgical treatment. GPR56 is a vital G protein-coupled receptor and its role in T lymphocytes has received considerable attention. However, its function in B cells remains unclear. This study aimed to investigate the significance of GPR56 in LUAD. We found that GPR56 exhibited a significant increase in circulating plasmablasts and a decrease in new memory B cells. GPR56 expression in B cells was significantly reduced after LPS stimulation and the proportion of HLA-DR+ and CD40+ proportions were also decreased in GPR56+ B cells after stimulation. Additionally, GPR56 exhibited significant down-regulation in circulating B cell subsets of early-stage LUAD patients, and there were significant correlations between GPR56+ B cell subsets and tumour markers. In conclusion, GPR56 could reflect the hypoactivation state of B cells and the decreased proportion of GPR56+ B cell subset in LUAD patients can signify the active humoral immunity in vivo. The expression of GPR56 in B cells could potentially hold value in the early diagnosis of LUAD.