Immune NetworkPub Date : 2024-10-21eCollection Date: 2024-10-01DOI: 10.4110/in.2024.24.e38
Ruby E Dawson, Brendan J Jenkins
{"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}
Immune NetworkPub 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
{"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}
{"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}
Immune NetworkPub Date : 2024-09-26eCollection Date: 2024-10-01DOI: 10.4110/in.2024.24.e35
Hyun-Sup Song, You-Me Kim
{"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}
Immune NetworkPub Date : 2024-08-19eCollection Date: 2024-10-01DOI: 10.4110/in.2024.24.e34
Min Hwa Shin, Eunha Oh, Dohsik Minn
{"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}
Immune NetworkPub 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
{"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}
Immune NetworkPub 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
{"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}
Immune NetworkPub Date : 2024-07-22eCollection Date: 2024-08-01DOI: 10.4110/in.2024.24.e31
Manisha Naskar, Hae Woong Choi
{"title":"A Dynamic Interplay of Innate Immune Responses During Urinary Tract Infection.","authors":"Manisha Naskar, Hae Woong Choi","doi":"10.4110/in.2024.24.e31","DOIUrl":"10.4110/in.2024.24.e31","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"24 4","pages":"e31"},"PeriodicalIF":4.3,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153895","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}
Immune NetworkPub Date : 2024-07-15eCollection Date: 2024-08-01DOI: 10.4110/in.2024.24.e30
Jin Soo Joo, Dongeun Lee, Jun Young Hong
{"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}
Immune NetworkPub Date : 2024-06-27eCollection Date: 2024-08-01DOI: 10.4110/in.2024.24.e29
Thamer A Hamdan
{"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}