Pub Date : 2024-10-21eCollection Date: 2024-10-01DOI: 10.4110/in.2024.24.e38
Ruby E Dawson, Brendan J Jenkins
Dysregulated activation of the innate immune system is a critical driver of chronic inflammation that is associated with at least 30% of all cancers. Innate immunity can also exert tumour-promoting effects (e.g. proliferation) directly on cancer cells in an intrinsic manner. Conversely, innate immunity can influence adaptive immunity-based anti-tumour immune responses via Ag-presenting dendritic cells that activate natural killer and cytotoxic T cells to eradicate tumours. While adaptive anti-tumour immunity has underpinned immunotherapy approaches with immune checkpoint inhibitors and chimeric Ag receptor-T cells, the clinical utility of innate immunity in cancer is underexplored. Innate immune responses are governed by pattern recognition receptors, which comprise several families, including Toll-like, nucleotide-binding oligomerization domain-containing (NOD)-like and absent-in-melanoma 2 (AIM2)-like receptors. Notably, a subset of NOD-like and AIM2-like receptors can form large multiprotein "inflammasome" complexes which control maturation of biologically active IL-1β and IL-18 cytokines. Over the last decade, it has emerged that inflammasomes can coordinate contrasting pro- and anti-tumour responses in cancer and non-cancer (e.g. immune, stromal) cells. Considering the importance of inflammasomes to the net output of innate immune responses, here we provide an overview and discuss recent advancements on the diverse role of inflammasomes in cancer that have underpinned their potential targeting in diverse malignancies.
{"title":"The Role of Inflammasome-Associated Innate Immune Receptors in Cancer.","authors":"Ruby E Dawson, Brendan J Jenkins","doi":"10.4110/in.2024.24.e38","DOIUrl":"https://doi.org/10.4110/in.2024.24.e38","url":null,"abstract":"<p><p>Dysregulated activation of the innate immune system is a critical driver of chronic inflammation that is associated with at least 30% of all cancers. Innate immunity can also exert tumour-promoting effects (e.g. proliferation) directly on cancer cells in an intrinsic manner. Conversely, innate immunity can influence adaptive immunity-based anti-tumour immune responses via Ag-presenting dendritic cells that activate natural killer and cytotoxic T cells to eradicate tumours. While adaptive anti-tumour immunity has underpinned immunotherapy approaches with immune checkpoint inhibitors and chimeric Ag receptor-T cells, the clinical utility of innate immunity in cancer is underexplored. Innate immune responses are governed by pattern recognition receptors, which comprise several families, including Toll-like, nucleotide-binding oligomerization domain-containing (NOD)-like and absent-in-melanoma 2 (AIM2)-like receptors. Notably, a subset of NOD-like and AIM2-like receptors can form large multiprotein \"inflammasome\" complexes which control maturation of biologically active IL-1β and IL-18 cytokines. Over the last decade, it has emerged that inflammasomes can coordinate contrasting pro- and anti-tumour responses in cancer and non-cancer (e.g. immune, stromal) cells. Considering the importance of inflammasomes to the net output of innate immune responses, here we provide an overview and discuss recent advancements on the diverse role of inflammasomes in cancer that have underpinned their potential targeting in diverse malignancies.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"24 5","pages":"e38"},"PeriodicalIF":4.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-16eCollection Date: 2024-10-01DOI: 10.4110/in.2024.24.e37
Kun Hee Lee, Jin Seok Woo, Ha Yeon Jeong, Jeong Won Choi, Chul Hwan Bang, Jeehee Youn, Sung-Hwan Park, Mi-La Cho
Systemic sclerosis (SS) is an autoimmune disease and pathological mechanisms of SS are unclear. In this study, we investigated the role of T cells in the progression of SS using SKG mice and humanized mice. SKG mice have a spontaneous point mutation in ZAP70. We induced scleroderma in SKG mice and a humanized SS mouse model to assess whether T cell-mediated immune responses induce SS. As a result, we found increased dermal thickness, fibrosis, and lymphocyte infiltration in skin tissue in SKG SS mice compared to BALB/c mice (control). Also, blood cytokine level, including IL-4- and IFN-α which are produced by CD4+ T cells via STIM1/STING/STAT6/IRF3 signaling pathways, were increased in SKG mice. Interestingly, skin fibrosis was reduced by inhibiting STING pathway in skin fibroblast. Next, we demonstrated the pathophysiological role of IL-4 and IFN-α in skin fibrosis using a humanized SS mouse model and found increased IL-4- and IFN-α-producing CD4+ T cells and fibrosis. In this study, we found that STING-induced production of IL-4- and type I IFN by CD4+ T cells is a key factor in mouse model and humanized mouse model of SS. Our findings suggest that the STING/STAT6/IRF3 signaling pathways are potential therapeutic targets in SS.
系统性硬化症(SS)是一种自身免疫性疾病,其病理机制尚不清楚。在这项研究中,我们利用 SKG 小鼠和人源化小鼠研究了 T 细胞在 SS 进展过程中的作用。SKG 小鼠的 ZAP70 存在自发点突变。我们在 SKG 小鼠和人源化 SS 小鼠模型中诱导硬皮病,以评估 T 细胞介导的免疫反应是否会诱导 SS。结果我们发现,与 BALB/c 小鼠(对照组)相比,SKG SS 小鼠皮肤组织中的真皮厚度、纤维化和淋巴细胞浸润增加。此外,SKG 小鼠血液中的细胞因子水平,包括 CD4+ T 细胞通过 STIM1/STING/STAT6/IRF3 信号通路产生的 IL-4- 和 IFN-α,也有所增加。有趣的是,抑制皮肤成纤维细胞中的 STING 通路可减少皮肤纤维化。接着,我们利用人源化 SS 小鼠模型证明了 IL-4 和 IFN-α 在皮肤纤维化中的病理生理作用,并发现分泌 IL-4 和 IFN-α 的 CD4+ T 细胞增多和纤维化。在这项研究中,我们发现 STING 诱导 CD4+ T 细胞产生 IL-4- 和 I 型 IFN 是 SS 小鼠模型和人源化小鼠模型的一个关键因素。我们的研究结果表明,STING/STAT6/IRF3 信号通路是 SS 的潜在治疗靶点。
{"title":"STING-STAT6 Signaling Pathway Promotes IL-4<sup>+</sup> and IFN-α<sup>+</sup> Fibrotic T Cell Activation and Exacerbates Scleroderma in SKG Mice.","authors":"Kun Hee Lee, Jin Seok Woo, Ha Yeon Jeong, Jeong Won Choi, Chul Hwan Bang, Jeehee Youn, Sung-Hwan Park, Mi-La Cho","doi":"10.4110/in.2024.24.e37","DOIUrl":"https://doi.org/10.4110/in.2024.24.e37","url":null,"abstract":"<p><p>Systemic sclerosis (SS) is an autoimmune disease and pathological mechanisms of SS are unclear. In this study, we investigated the role of T cells in the progression of SS using SKG mice and humanized mice. SKG mice have a spontaneous point mutation in ZAP70. We induced scleroderma in SKG mice and a humanized SS mouse model to assess whether T cell-mediated immune responses induce SS. As a result, we found increased dermal thickness, fibrosis, and lymphocyte infiltration in skin tissue in SKG SS mice compared to BALB/c mice (control). Also, blood cytokine level, including IL-4- and IFN-α which are produced by CD4<sup>+</sup> T cells via STIM1/STING/STAT6/IRF3 signaling pathways, were increased in SKG mice. Interestingly, skin fibrosis was reduced by inhibiting STING pathway in skin fibroblast. Next, we demonstrated the pathophysiological role of IL-4 and IFN-α in skin fibrosis using a humanized SS mouse model and found increased IL-4- and IFN-α-producing CD4<sup>+</sup> T cells and fibrosis. In this study, we found that STING-induced production of IL-4- and type I IFN by CD4<sup>+</sup> T cells is a key factor in mouse model and humanized mouse model of SS. Our findings suggest that the STING/STAT6/IRF3 signaling pathways are potential therapeutic targets in SS.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"24 5","pages":"e37"},"PeriodicalIF":4.3,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adult-onset immunodeficiency (AOID) is associated with the presence of anti-IFN-γ autoantibodies (auAbs). In disseminated nontuberculous mycobacterial (dNTM) infection with AOID, neutralization of IFN-γ by auAb may play a role in disease susceptibility, but other molecular mechanisms are likely to contribute. In this study, dNTM patients, including inactive, active but non-progressive and active, progressive cases were enrolled to measure plasma anti-IFN-γ auAb by ELISA and underwent whole-blood RNA sequencing. Healthy control individuals were also enrolled. Plasma IL-8 was then quantified to confirm transcriptomic analysis. Results revealed that anti-IFN-γ auAb titers were significantly increased in patients with active stage of disease. Gene expression could separate patients with active infection from individuals with no signs of infection (inactive patients and healthy controls). In active cases, there was over-expression of inflammatory pathways and under-expression of type-2 immunity pathways. Interestingly, increased levels of plasma IL-8 (p=0.0167) not only confirmed gene expression results but also correlated with the presence of neutrophilic dermatitis (p=0.0244). In conclusion, our findings highlight the value of anti-IFN-γ auAb titers for predicting disease reactivity and first propose IL-8 as a promising mediator to be further explored, given its correlation with skin reactive disease, a hallmark of active dNTM infection.
{"title":"Increased Inflammatory Responses in Patients With Active Disseminated Non-Tuberculous Mycobacterial Infection and High Anti-Interferon-Gamma Autoantibodies.","authors":"Pattaraporn Srisai, Chanchai Hongsa, Yothin Hinwan, Varis Manbenmad, Ploenchan Chetchotisakd, Siriluck Anunnatsiri, Kiatichai Faksri, Todsapol Techo, Kanin Salao, Steven W Edwards, Arnone Nithichanon","doi":"10.4110/in.2024.24.e36","DOIUrl":"https://doi.org/10.4110/in.2024.24.e36","url":null,"abstract":"<p><p>Adult-onset immunodeficiency (AOID) is associated with the presence of anti-IFN-γ autoantibodies (auAbs). In disseminated nontuberculous mycobacterial (dNTM) infection with AOID, neutralization of IFN-γ by auAb may play a role in disease susceptibility, but other molecular mechanisms are likely to contribute. In this study, dNTM patients, including inactive, active but non-progressive and active, progressive cases were enrolled to measure plasma anti-IFN-γ auAb by ELISA and underwent whole-blood RNA sequencing. Healthy control individuals were also enrolled. Plasma IL-8 was then quantified to confirm transcriptomic analysis. Results revealed that anti-IFN-γ auAb titers were significantly increased in patients with active stage of disease. Gene expression could separate patients with active infection from individuals with no signs of infection (inactive patients and healthy controls). In active cases, there was over-expression of inflammatory pathways and under-expression of type-2 immunity pathways. Interestingly, increased levels of plasma IL-8 (p=0.0167) not only confirmed gene expression results but also correlated with the presence of neutrophilic dermatitis (p=0.0244). In conclusion, our findings highlight the value of anti-IFN-γ auAb titers for predicting disease reactivity and first propose IL-8 as a promising mediator to be further explored, given its correlation with skin reactive disease, a hallmark of active dNTM infection.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"24 5","pages":"e36"},"PeriodicalIF":4.3,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-26eCollection Date: 2024-10-01DOI: 10.4110/in.2024.24.e35
Hyun-Sup Song, You-Me Kim
Plasma cells (PCs) constitute a small proportion of B cells, limiting their biochemical characterization. An in vitro culture system that reliably generates PCs could provide an alternative method to obtain PCs for further analysis and manipulation. To date, most in vitro PC differentiation methods rely on B cell receptor (BCR)-independent stimulants, including TLR ligands, CD40L, and cytokines. However, these methods do not fully recapitulate the natural T cell-dependent PC differentiation process, in which BCR activation is the initial events. In this study, we established an efficient in vitro PC differentiation method incorporating BCR stimulation. Naïve B cells were first stimulated with anti-IgM and anti-CD40 Abs, followed by stimulation with various cytokines. By screening cytokines known to participate in PC differentiation in vivo, we identified that the combination of IL-4 and IL-5 induced the most efficient PC differentiation. The in vitro generated PCs highly expressed PC-associated surface markers and regulatory genes. Additionally, they secreted high amounts of IgM and IgG Abs. Moreover, retroviral transduction of B cells resulted in efficient target gene expression in PCs. Our new method closely mimics natural PC differentiation and effectively generates a large quantity of PCs for various applications, including elucidating the molecular mechanisms underlying PC differentiation.
浆细胞(PCs)在 B 细胞中所占比例很小,这限制了对其进行生化鉴定。一种能可靠生成 PC 的体外培养系统可提供另一种获得 PC 的方法,用于进一步分析和操作。迄今为止,大多数体外 PC 分化方法都依赖于不依赖 B 细胞受体(BCR)的刺激物,包括 TLR 配体、CD40L 和细胞因子。然而,这些方法并不能完全再现依赖于 T 细胞的 PC 自然分化过程,在这一过程中,BCR 激活是初始事件。在这项研究中,我们建立了一种结合 BCR 刺激的高效体外 PC 分化方法。首先用抗 IgM 和抗 CD40 Abs 刺激新生 B 细胞,然后用各种细胞因子刺激。通过筛选已知参与体内PC分化的细胞因子,我们发现IL-4和IL-5的组合能诱导最有效的PC分化。体外生成的 PC 高度表达与 PC 相关的表面标记和调控基因。此外,它们还分泌大量的 IgM 和 IgG Abs。此外,逆转录病毒转导 B 细胞可使 PC 中的靶基因高效表达。我们的新方法近似于自然 PC 分化,能有效地产生大量 PC,可用于各种应用,包括阐明 PC 分化的分子机制。
{"title":"Efficient <i>In Vitro</i> Plasma Cell Differentiation by B Cell Receptor Activation and Cytokine Stimulation.","authors":"Hyun-Sup Song, You-Me Kim","doi":"10.4110/in.2024.24.e35","DOIUrl":"https://doi.org/10.4110/in.2024.24.e35","url":null,"abstract":"<p><p>Plasma cells (PCs) constitute a small proportion of B cells, limiting their biochemical characterization. An <i>in vitro</i> culture system that reliably generates PCs could provide an alternative method to obtain PCs for further analysis and manipulation. To date, most <i>in vitro</i> PC differentiation methods rely on B cell receptor (BCR)-independent stimulants, including TLR ligands, CD40L, and cytokines. However, these methods do not fully recapitulate the natural T cell-dependent PC differentiation process, in which BCR activation is the initial events. In this study, we established an efficient <i>in vitro</i> PC differentiation method incorporating BCR stimulation. Naïve B cells were first stimulated with anti-IgM and anti-CD40 Abs, followed by stimulation with various cytokines. By screening cytokines known to participate in PC differentiation <i>in vivo</i>, we identified that the combination of IL-4 and IL-5 induced the most efficient PC differentiation. The <i>in vitro</i> generated PCs highly expressed PC-associated surface markers and regulatory genes. Additionally, they secreted high amounts of IgM and IgG Abs. Moreover, retroviral transduction of B cells resulted in efficient target gene expression in PCs. Our new method closely mimics natural PC differentiation and effectively generates a large quantity of PCs for various applications, including elucidating the molecular mechanisms underlying PC differentiation.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"24 5","pages":"e35"},"PeriodicalIF":4.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-19eCollection Date: 2024-10-01DOI: 10.4110/in.2024.24.e34
Min Hwa Shin, Eunha Oh, Dohsik Minn
NK cells are specialized immune effector cells crucial for triggering immune responses against aberrant cells. Although recent advancements have concentrated on creating or releasing T-cell responses specific to tumor Ags, the clinical advantages of this approach have been limited to certain groups of patients and tumor types. This emphasizes the need for alternative strategies. One pioneering approach involves broadening and enhancing anti-tumor immune responses by targeting innate immunity. Consequently, the advent of bi-, tri-, and multi-specific Abs has facilitated the advancement of targeted cancer immunotherapies by redirecting immune effector cells to eradicate tumor cells. These Abs enable the simultaneous binding of surface Ags on tumor cells and the activation of receptors on innate immune cells, such as NK cells, with the ability to facilitate Ab-dependent cellular cytotoxicity to enhance their immunotherapeutic effectiveness in patients with solid tumors. Here, we review the recent advances in NK cell engagers (NKCEs) focusing on NK cell-activating receptors CD16A and NKp46. In addition, we provide an overview of the ongoing clinical trials investigating the safety, efficacy, and potential of NKCEs.
NK 细胞是特化的免疫效应细胞,对触发针对异常细胞的免疫反应至关重要。尽管最近的研究进展集中于产生或释放针对肿瘤Ags的特异性T细胞反应,但这种方法的临床优势仅限于某些患者群体和肿瘤类型。这就强调了替代策略的必要性。一种开创性的方法是通过针对先天性免疫来扩大和增强抗肿瘤免疫反应。因此,双特异性抗体、三特异性抗体和多特异性抗体的出现,通过重新引导免疫效应细胞消灭肿瘤细胞,促进了靶向癌症免疫疗法的发展。这些Abs能同时与肿瘤细胞表面的Ags结合,并激活先天性免疫细胞(如NK细胞)上的受体,从而促进Abs依赖性细胞毒性,增强对实体瘤患者的免疫治疗效果。在此,我们回顾了 NK 细胞激活剂 (NKCE) 的最新进展,重点是 NK 细胞激活受体 CD16A 和 NKp46。此外,我们还概述了正在进行的研究 NKCEs 安全性、有效性和潜力的临床试验。
{"title":"Current Developments in NK Cell Engagers for Cancer Immunotherapy: Focus on CD16A and NKp46.","authors":"Min Hwa Shin, Eunha Oh, Dohsik Minn","doi":"10.4110/in.2024.24.e34","DOIUrl":"https://doi.org/10.4110/in.2024.24.e34","url":null,"abstract":"<p><p>NK cells are specialized immune effector cells crucial for triggering immune responses against aberrant cells. Although recent advancements have concentrated on creating or releasing T-cell responses specific to tumor Ags, the clinical advantages of this approach have been limited to certain groups of patients and tumor types. This emphasizes the need for alternative strategies. One pioneering approach involves broadening and enhancing anti-tumor immune responses by targeting innate immunity. Consequently, the advent of bi-, tri-, and multi-specific Abs has facilitated the advancement of targeted cancer immunotherapies by redirecting immune effector cells to eradicate tumor cells. These Abs enable the simultaneous binding of surface Ags on tumor cells and the activation of receptors on innate immune cells, such as NK cells, with the ability to facilitate Ab-dependent cellular cytotoxicity to enhance their immunotherapeutic effectiveness in patients with solid tumors. Here, we review the recent advances in NK cell engagers (NKCEs) focusing on NK cell-activating receptors CD16A and NKp46. In addition, we provide an overview of the ongoing clinical trials investigating the safety, efficacy, and potential of NKCEs.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"24 5","pages":"e34"},"PeriodicalIF":4.3,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-14eCollection Date: 2024-10-01DOI: 10.4110/in.2024.24.e33
Reinhart Speeckaert, Arno Belpaire, Jo Lambert, Marijn Speeckaert, Nanja van Geel
In recent years, there have been significant breakthroughs in the identification of immunological components of skin diseases and in the development of immunomodulatory drugs. Novel therapies create exciting prospects for personalized care. This article provides an overview of the role played by Th1, Th2, Th17, and follicular Th pathways in the most common skin diseases. Additionally, it elucidates the impact of current and upcoming treatments on each of these signaling cascades. Skin diseases predominantly influenced by a single dominant Th pathway such as psoriasis and atopic dermatitis are well-suited for biologics. However, in many other disorders a complex interplay between different immune pathways exists. This can lead to inconsistent efficacy of biologics based on individual patient profiles. In case of activation of several Th pathways, it may be more suitable to consider conventional therapies or JAK inhibitors. Increasing immunological insights have transitioned from laboratory research to practical applications, a trend that is expected to continue growing in the future.
{"title":"Th Pathways in Immune-Mediated Skin Disorders: A Guide for Strategic Treatment Decisions.","authors":"Reinhart Speeckaert, Arno Belpaire, Jo Lambert, Marijn Speeckaert, Nanja van Geel","doi":"10.4110/in.2024.24.e33","DOIUrl":"https://doi.org/10.4110/in.2024.24.e33","url":null,"abstract":"<p><p>In recent years, there have been significant breakthroughs in the identification of immunological components of skin diseases and in the development of immunomodulatory drugs. Novel therapies create exciting prospects for personalized care. This article provides an overview of the role played by Th1, Th2, Th17, and follicular Th pathways in the most common skin diseases. Additionally, it elucidates the impact of current and upcoming treatments on each of these signaling cascades. Skin diseases predominantly influenced by a single dominant Th pathway such as psoriasis and atopic dermatitis are well-suited for biologics. However, in many other disorders a complex interplay between different immune pathways exists. This can lead to inconsistent efficacy of biologics based on individual patient profiles. In case of activation of several Th pathways, it may be more suitable to consider conventional therapies or JAK inhibitors. Increasing immunological insights have transitioned from laboratory research to practical applications, a trend that is expected to continue growing in the future.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"24 5","pages":"e33"},"PeriodicalIF":4.3,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-12eCollection Date: 2024-08-01DOI: 10.4110/in.2024.24.e32
Bo-Gyu Kim, Hoon Sik Choi, Yong-Ho Choe, Hyun Min Jeon, Ji Yeon Heo, Yun-Hong Cheon, Ki Mun Kang, Sang-Il Lee, Bae Kwon Jeong, Mingyo Kim
Low-dose radiotherapy (LDRT) has been explored as a treatment option for various inflammatory diseases; however, its application in the context of rheumatoid arthritis (RA) is lacking. This study aimed to elucidate the mechanism underlying LDRT-based treatment for RA and standardize it. LDRT reduced the total numbers of immune cells, but increased the apoptotic CD4+ T and B220+ B cells, in the draining lymph nodes of collagen induced arthritis and K/BxN models. In addition, it significantly reduced the severity of various pathological manifestations, including bone destruction, cartilage erosion, and swelling of hind limb ankle. Post-LDRT, the proportion of apoptotic CD4+ T and CD19+ B cells increased significantly in the PBMCs derived from human patients with RA. LDRT showed a similar effect in fibroblast-like synoviocytes as well. In conclusion, we report that LDRT induces apoptosis in immune cells and fibro-blast-like synoviocytes, contributing to attenuation of arthritis.
{"title":"Low-Dose Radiotherapy Attenuates Experimental Autoimmune Arthritis by Inducing Apoptosis of Lymphocytes and Fibroblast-Like Synoviocytes.","authors":"Bo-Gyu Kim, Hoon Sik Choi, Yong-Ho Choe, Hyun Min Jeon, Ji Yeon Heo, Yun-Hong Cheon, Ki Mun Kang, Sang-Il Lee, Bae Kwon Jeong, Mingyo Kim","doi":"10.4110/in.2024.24.e32","DOIUrl":"10.4110/in.2024.24.e32","url":null,"abstract":"<p><p>Low-dose radiotherapy (LDRT) has been explored as a treatment option for various inflammatory diseases; however, its application in the context of rheumatoid arthritis (RA) is lacking. This study aimed to elucidate the mechanism underlying LDRT-based treatment for RA and standardize it. LDRT reduced the total numbers of immune cells, but increased the apoptotic CD4<sup>+</sup> T and B220<sup>+</sup> B cells, in the draining lymph nodes of collagen induced arthritis and K/BxN models. In addition, it significantly reduced the severity of various pathological manifestations, including bone destruction, cartilage erosion, and swelling of hind limb ankle. Post-LDRT, the proportion of apoptotic CD4<sup>+</sup> T and CD19<sup>+</sup> B cells increased significantly in the PBMCs derived from human patients with RA. LDRT showed a similar effect in fibroblast-like synoviocytes as well. In conclusion, we report that LDRT induces apoptosis in immune cells and fibro-blast-like synoviocytes, contributing to attenuation of arthritis.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"24 4","pages":"e32"},"PeriodicalIF":4.3,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-22eCollection Date: 2024-08-01DOI: 10.4110/in.2024.24.e31
Manisha Naskar, Hae Woong Choi
Urinary tract infections (UTIs) represent one of the most prevalent bacterial infections globally, manifesting in diverse clinical phenotypes with varying degrees of severity and complications. The mechanisms underlying UTIs are gradually being elucidated, leading to an enhanced understanding of the immune responses involved. Innate immune cells play a crucial defensive role against uropathogenic bacteria through various mechanisms. Despite their significant contributions to host defense, these cells often fail to achieve complete clearance of uropathogens, necessitating the frequent prescription of antibiotics for UTI patients. However, the persistence of infections and related pathological symptoms in the absence of innate immune cells in animal models underscore the importance of innate immunity in UTIs. Therefore, the host protective functions of innate immune cells, including neutrophils, macrophages, mast cells, NK cells, innate lymphoid cells, and γδ T cells, are delicately coordinated and timely regulated by a variety of cytokines to ensure successful pathogen clearance.
尿路感染(UTI)是全球最常见的细菌感染之一,临床表现多种多样,严重程度和并发症也各不相同。尿路感染的发病机制正逐渐被阐明,从而加深了人们对相关免疫反应的了解。先天性免疫细胞通过各种机制对尿路致病菌发挥着重要的防御作用。尽管先天性免疫细胞对宿主防御做出了重要贡献,但它们往往无法完全清除尿路病原体,因此尿路感染患者必须经常使用抗生素。然而,在动物模型中,在先天性免疫细胞缺失的情况下,感染和相关病理症状仍会持续,这凸显了先天性免疫在UTI 中的重要性。因此,先天性免疫细胞(包括中性粒细胞、巨噬细胞、肥大细胞、NK 细胞、先天性淋巴细胞和 γδ T 细胞)对宿主的保护功能受到各种细胞因子的微妙协调和及时调控,以确保成功清除病原体。
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Pub Date : 2024-07-15eCollection Date: 2024-08-01DOI: 10.4110/in.2024.24.e30
Jin Soo Joo, Dongeun Lee, Jun Young Hong
Pregnancy represents an immunological paradox where the maternal immune system must tolerate the semi-allogeneic fetus expressing paternally-derived Ags. Accumulating evidence over decades has revealed that successful pregnancy requires the active development of robust immune tolerance mechanisms. This review outlines the multi-layered processes that establish fetomaternal tolerance, including the physical barrier of the placenta, restricted chemokine-mediated leukocyte trafficking, lack of sufficient alloantigen presentation, the presence of immunosuppressive regulatory T cells and tolerogenic decidual natural killer cells, expression of immune checkpoint molecules, specific glycosylation patterns conferring immune evasion, and unique metabolic/hormonal modulations. Interestingly, many of the strategies that enable fetal tolerance parallel those employed by cancer cells to promote angiogenesis, invasion, and immune escape. As such, further elucidating the mechanistic underpinnings of fetal-maternal tolerance may reciprocally provide insights into developing novel cancer immunotherapies as well as understanding the pathogenesis of gestational complications linked to dysregulated tolerance processes.
妊娠是一个免疫学悖论,母体免疫系统必须耐受表达父源抗体的半异体胎儿。几十年来积累的证据表明,成功妊娠需要积极发展强大的免疫耐受机制。本综述概述了建立胎儿-母体耐受性的多层次过程,包括胎盘的物理屏障、趋化因子介导的白细胞迁移受限、缺乏足够的同种抗原呈递、存在免疫抑制调节性 T 细胞和耐受性蜕膜自然杀伤细胞、免疫检查点分子的表达、赋予免疫逃避功能的特定糖基化模式以及独特的代谢/激素调节。有趣的是,使胎儿产生耐受性的许多策略与癌细胞促进血管生成、侵袭和免疫逃逸的策略相似。因此,进一步阐明胎儿-母体耐受性的机理基础可为开发新型癌症免疫疗法以及了解与耐受性失调过程相关的妊娠并发症的发病机制提供有益的启示。
{"title":"Multi-Layered Mechanisms of Immunological Tolerance at the Maternal-Fetal Interface.","authors":"Jin Soo Joo, Dongeun Lee, Jun Young Hong","doi":"10.4110/in.2024.24.e30","DOIUrl":"10.4110/in.2024.24.e30","url":null,"abstract":"<p><p>Pregnancy represents an immunological paradox where the maternal immune system must tolerate the semi-allogeneic fetus expressing paternally-derived Ags. Accumulating evidence over decades has revealed that successful pregnancy requires the active development of robust immune tolerance mechanisms. This review outlines the multi-layered processes that establish fetomaternal tolerance, including the physical barrier of the placenta, restricted chemokine-mediated leukocyte trafficking, lack of sufficient alloantigen presentation, the presence of immunosuppressive regulatory T cells and tolerogenic decidual natural killer cells, expression of immune checkpoint molecules, specific glycosylation patterns conferring immune evasion, and unique metabolic/hormonal modulations. Interestingly, many of the strategies that enable fetal tolerance parallel those employed by cancer cells to promote angiogenesis, invasion, and immune escape. As such, further elucidating the mechanistic underpinnings of fetal-maternal tolerance may reciprocally provide insights into developing novel cancer immunotherapies as well as understanding the pathogenesis of gestational complications linked to dysregulated tolerance processes.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"24 4","pages":"e30"},"PeriodicalIF":4.3,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-27eCollection Date: 2024-08-01DOI: 10.4110/in.2024.24.e29
Thamer A Hamdan
NK cells belong to innate lymphoid cells and able to eliminate infected cells and tumor cells. NK cells play a valuable role in controlling viral infections. Also, they have the potential to shape the adaptive immunity via a unique crosstalk with the different immune cells. Murine models are important tools for delineating the immunological phenomena in viral infection. To decipher the immunological virus-host interactions, two major infection models are being investigated in mice regarding NK cell-mediated recognition: murine cytomegalovirus (MCMV) and lymphocytic choriomeningitis virus (LCMV). In this review, we recapitulate recent findings regarding the multifaceted role of NK cells in controlling LCMV and MCMV infections and outline the exquisite interplay between NK cells and other immune cells in these two settings. Considering that, infections with MCMV and LCMV recapitulates many physiopathological characteristics of human cytomegalovirus infection and chronic virus infections respectively, this study will extend our understanding of NK cells biology in interactions between the virus and its natural host.
NK 细胞属于先天性淋巴细胞,能够清除受感染的细胞和肿瘤细胞。NK 细胞在控制病毒感染方面发挥着重要作用。此外,NK 细胞还能通过与不同免疫细胞之间的独特串扰,形成适应性免疫。小鼠模型是描述病毒感染免疫现象的重要工具。为了破译病毒与宿主之间的免疫学相互作用,目前正在小鼠中研究 NK 细胞介导识别的两种主要感染模型:鼠巨细胞病毒(MCMV)和淋巴细胞性脉络膜炎病毒(LCMV)。在这篇综述中,我们回顾了有关 NK 细胞在控制 LCMV 和 MCMV 感染中的多方面作用的最新发现,并概述了 NK 细胞和其他免疫细胞在这两种情况下的微妙相互作用。考虑到 MCMV 和 LCMV 感染分别再现了人类巨细胞病毒感染和慢性病毒感染的许多生理病理特征,本研究将扩展我们对 NK 细胞在病毒与其自然宿主相互作用中的生物学作用的理解。
{"title":"The Multifaceted Roles of NK Cells in the Context of Murine Cytomegalovirus and Lymphocytic Choriomeningitis Virus Infections.","authors":"Thamer A Hamdan","doi":"10.4110/in.2024.24.e29","DOIUrl":"10.4110/in.2024.24.e29","url":null,"abstract":"<p><p>NK cells belong to innate lymphoid cells and able to eliminate infected cells and tumor cells. NK cells play a valuable role in controlling viral infections. Also, they have the potential to shape the adaptive immunity via a unique crosstalk with the different immune cells. Murine models are important tools for delineating the immunological phenomena in viral infection. To decipher the immunological virus-host interactions, two major infection models are being investigated in mice regarding NK cell-mediated recognition: murine cytomegalovirus (MCMV) and lymphocytic choriomeningitis virus (LCMV). In this review, we recapitulate recent findings regarding the multifaceted role of NK cells in controlling LCMV and MCMV infections and outline the exquisite interplay between NK cells and other immune cells in these two settings. Considering that, infections with MCMV and LCMV recapitulates many physiopathological characteristics of human cytomegalovirus infection and chronic virus infections respectively, this study will extend our understanding of NK cells biology in interactions between the virus and its natural host.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"24 4","pages":"e29"},"PeriodicalIF":4.3,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}