Current Opinion in Immunology最新文献

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The choroid plexus: a command center for brain–body communication during inflammation

IF 6.6 2区医学 Q1 IMMUNOLOGY

Current Opinion in Immunology

Pub Date : 2025-02-27 DOI: 10.1016/j.coi.2025.102540

Huixin Xu, Christine Hehnly, Maria K Lehtinen

During brain inflammation, rigorous regulation of brain–body communication is required for sufficient, but not excessive, immune activation. As a crucial neuroimmune interface, the choroid plexus (ChP) epithelium serves as both a physical barrier between blood and cerebrospinal fluid (CSF) and a gateway allowing peripheral immune cell entry into the central nervous system (CNS). Recent years have witnessed increasing investigations of ChP events during brain inflammation. Here, we contextualize new findings with established ChP core functions, including CSF secretion and blood–CSF barrier regulation. We reason that the ChP is an organ where immune and nonimmune cells collaborate to defend the CNS. We discuss the pertinent mechanisms and the implications for neurologic disease etiology and treatment. Finally, we discuss outstanding questions for this rapidly expanding field and suggest key technologies and experimental steps to elucidate the full range of ChP functions during neuroinflammatory conditions, such as infection, injury, and aging.

引用次数: 0

Primary atopic disorders: inborn errors of immunity causing severe allergic disease

IF 6.6 2区医学 Q1 IMMUNOLOGY

Current Opinion in Immunology

Pub Date : 2025-02-27 DOI: 10.1016/j.coi.2025.102538

Maryam Vaseghi-Shanjani , Simran Samra , Pariya Yousefi , Catherine M Biggs , Stuart E Turvey

Allergic diseases, including asthma, allergic rhinitis, atopic dermatitis, and food allergies, are driven by dysregulated immune responses, often involving IgE-mediated mast cell and basophil activation, Th2 inflammation, and epithelial dysfunction. While environmental factors are well-known contributors, the genetic components underpinning these conditions are increasingly understood. Traditionally viewed as polygenic multifactorial disorders, allergic diseases can also be caused by single-gene defects affecting the immune system and skin epithelial barrier, leading to profoundly dysregulated allergic responses. These monogenic allergic disorders are collectively referred to as primary atopic disorders or PADs. To date, over 48 single-gene defects have been established to cause PADs. This review highlights (i) the significance of PADs, (ii) the biological pathways involved in the pathogenesis of PADs, (iii) clinical strategies to differentiate PADs from their much more common polygenic counterparts, and (iv) diagnostic strategies for PADs.

引用次数: 0

More X’s, more problems: how contributions from the X chromosomes enhance female predisposition for autoimmunity

IF 6.6 2区医学 Q1 IMMUNOLOGY

Current Opinion in Immunology

Pub Date : 2025-02-27 DOI: 10.1016/j.coi.2025.102543

Claudia D Lovell, Montserrat C Anguera

Many autoimmune diseases exhibit a strong female bias. While sex hormones may influence sex bias in disease, recent studies suggest that the X chromosome itself directly contributes to female-biased susceptibility to autoimmunity. Females with two X chromosomes utilize X Chromosome Inactivation (XCI) to silence gene expression from one X chromosome, equalizing expression between the sexes. The X chromosome is highly enriched with immune-related genes, and recent work indicates that the fidelity of XCI maintenance in lymphocytes from female systemic lupus erythematosus patients is compromised, suggesting that aberrant X-linked gene expression contributes to autoimmune phenotypes. XCI is initiated and maintained by the long noncoding RNA XIST/Xist through its interactions with the inactive X chromosome and numerous interacting proteins, and recent studies also implicate XIST/Xist RNA in driving endosomal Toll-like receptor signaling and XIST/Xist RNA-protein complexes in serving as a source of autoantigens to respectively drive autoimmunity. Here, we will review these three distinct pathways that underscore the significance of X-linked genetics for understanding the origins of the female bias in autoimmune disease.

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引用次数: 0

Defenders or defectors: mucosal-associated invariant T cells in autoimmune diseases

IF 6.6 2区医学 Q1 IMMUNOLOGY

Current Opinion in Immunology

Pub Date : 2025-02-27 DOI: 10.1016/j.coi.2025.102542

Mitchell Kronenberg , Thomas Riffelmacher

Mucosal-associated invariant T (MAIT) cells recognize microbial riboflavin metabolites presented by MR1, a major histocompatibility complex class I–like protein. Activated MAIT cells produce cytokines such as interferon gamma (IFNγ), tumor necrosis factor, and interleukin-17; they traffic to sites of infection and participate in protective responses. They are absent in germ-free mice and are dependent on microbes. MAIT cells not only respond to infections but also have been analyzed in various autoimmune diseases. A trend is that in autoimmune disease, MAIT cells are decreased in the circulation and increased and activated or exhausted in the site of inflammation. Despite a possible pathogenic role, publications show MAIT cells also can function in tissue repair. Mouse autoimmune disease models support the presence of both these MAIT cell functions. The signals driving the balance of inflammatory and tissue repair in MAIT cell responses remain to be fully elucidated.

引用次数: 0

Friends close, enemies closer: the complex role of the microbiome in antitumor immunity

IF 6.6 2区医学 Q1 IMMUNOLOGY

Current Opinion in Immunology

Pub Date : 2025-02-27 DOI: 10.1016/j.coi.2025.102537

Dipyaman Patra , Gagan Dev , Timothy W Hand , Abigail Overacre-Delgoffe

Immunotherapy has achieved remarkable advances in cancer treatment by harnessing the immune system to combat tumors, yet its effectiveness remains inconsistent across patients and tumor types. The microbiota, a diverse assemblage of microorganisms residing at host barrier surfaces, is pivotal in shaping immune responses. This review explores the direct and indirect mechanisms via which the microbiota modulates antitumor immune responses both locally within the tumor microenvironment and systemically by affecting distant tumors. We discuss recent findings linking microbiota-derived metabolites and microbiota-derived antigens with antitumor immunity and immunotherapy response. Additionally, we discuss recent advances in microbiome-based therapies, including fecal microbiota transplantation. We propose the use and development of new analytical techniques to further characterize the complex functions and interactions between the microbiome and immune system. To conclude, we outline recommendations for future research and therapeutic approaches to leverage the microbiome to improve current immunotherapies.

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引用次数: 0

T cell–B cell interactions in human autoimmune diseases

IF 6.6 2区医学 Q1 IMMUNOLOGY

Current Opinion in Immunology

Pub Date : 2025-02-27 DOI: 10.1016/j.coi.2025.102539

John M Sowerby, Deepak A Rao

Activation of autoreactive B cells and production of specific autoantibodies are hallmark features of many autoimmune diseases. B cell differentiation into antibody-secreting cells typically requires help from cognate T cells, which provide both cytokines and cell surface signals in an intricate intercellular interaction. A range of T cells can provide this help to B cells, including T follicular helper cells in follicles of secondary lymphoid organs, as well as T peripheral helper cells, which accumulate within inflamed target tissues in autoimmune diseases. Here, we discuss recent observations about the phenotypes of B cell–helper T cells that accumulate in inflamed tissues and in circulation of patients with autoimmune diseases, the correlations between B cell–helper T cells and B cells in these tissues, and key mediators of productive T cell–B cell interactions, with a focus on mediators that are being targeted therapeutically. Understanding the scope of B cell–helper T cells and their functions will improve our ability to quantify and track pathologic T cell–B cell interactions in human autoimmune diseases and may highlight critical mediators that can be targeted to suppress these interactions therapeutically.

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引用次数: 0

Sensory neurons on guard: roles in pathogen defense and host immunity

IF 6.6 2区医学 Q1 IMMUNOLOGY

Current Opinion in Immunology

Pub Date : 2025-02-26 DOI: 10.1016/j.coi.2025.102541

Ozge Erdogan , Xiao-Qian Hu , Isaac M Chiu

The nervous system, like the immune system, constantly interfaces with the environment, encountering threats, including pathogens. Recent discoveries reveal an emerging role for sensory neurons in host defense and immunity. Sensory neurons detect infections either by directly sensing microbial signals or through immune mediators. Beyond pathogen detection, they modulate immune responses and local inflammation by interacting with immune cells, influencing inflammation and pathogen clearance. Additionally, sensory neurons trigger protective reflexes — such as pain, coughing, sneezing, and itching — that can help expel pathogens but may also facilitate their spread. Sensory neurons may also encode and shape long-term immunity. Understanding the roles of neurons in pathogen defense could offer new insights into infectious diseases and highlight therapeutic opportunities for immune modulation.

引用次数: 0

Lymphatic messengers: Non-antigen soluble mediators from diseased tissues to draining lymph nodes

IF 6.6 2区医学 Q1 IMMUNOLOGY

Current Opinion in Immunology

Pub Date : 2025-02-05 DOI: 10.1016/j.coi.2025.102536

Mir J Howlader , Mehdi Rashighi , Laura Santambrogio , Theresa T Lu

Tissues deliver not only antigens and cells via afferent lymphatics to draining lymph nodes during immune responses but also deliver soluble molecules that reflect the state of the tissue. In autoimmune diseases, these signals from affected tissues can potentially impact the magnitude or other characteristics of autoimmune responses generated in lymph nodes. Here, we highlight recent studies illustrating the nature of these soluble signals relevant to lupus skin and in lymphatic fluid draining the gut in inflammatory bowel disease. We also highlight the role of lymph node stromal cells as recipients of lymph borne signals. Identifying the molecules delivered from the tissues and how exactly they modulate immune function in draining lymph nodes will help us to better understand aberrant immunity in disease.

引用次数: 0

Editorial overview: Framing the logic of type 2 immunity 编辑综述：构建 2 型免疫的逻辑。

IF 6.6 2区医学 Q1 IMMUNOLOGY

Current Opinion in Immunology

Pub Date : 2025-02-01 DOI: 10.1016/j.coi.2024.102523

Caroline L Sokol , Rod A Rahimi

引用次数: 0

Patterns of bacterial viability governing noncanonical inflammasome activation 控制非典型炎性体活化的细菌活力模式。

IF 6.6 2区医学 Q1 IMMUNOLOGY

Current Opinion in Immunology

Pub Date : 2025-02-01 DOI: 10.1016/j.coi.2024.102512

Yuhua Shi , J Magarian Blander

Noncanonical inflammasomes are instrumental in defense against Gram-negative bacteria, activated primarily by bacterial lipopolysaccharide. This review examines commonalities and distinctions in noncanonical inflammasome activation either by virulence factor activity indicating cellular invasion or by detection of bacterial mRNA signaling the undesired presence of live bacteria in sterile tissue. These inflammasome triggers, alongside other examples discussed, reflect properties exclusive to live bacteria. The emerging picture underscores noncanonical inflammasome activation hinging on detection of indicators of bacterial viability such as the presence of certain molecules or activity of specific processes. The complex interpretation of combinatorial signals is essential for inflammasome activation according to the specific facet of infection confronting the host. Decoding these signals and their convergence on inflammasome activation will inform interventions and therapies for infectious diseases.

非典型炎性体在抵御革兰氏阴性细菌的过程中起着重要作用，主要由细菌脂多糖激活。这篇综述探讨了非典型炎症小体激活的共性和区别，它们或由表明细胞入侵的毒力因子活性激活，或由检测到表明无菌组织中存在活细菌的细菌 mRNA 激活。这些炎症小体触发器以及所讨论的其他例子都反映了活细菌独有的特性。新出现的情况强调，非规范炎性体的激活取决于对细菌存活指标的检测，如某些分子的存在或特定过程的活动。根据宿主所面临的感染的特定方面，对组合信号的复杂解读对于炎性体的激活至关重要。对这些信号的解码以及它们在炎症小体激活过程中的交汇将为传染病的干预和治疗提供依据。

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