Immunology letters最新文献

{"title":"Human dendritic cell differentiation in hematopoietic stem cell-transplanted NOG hFLT3L Tg/mFlt3 KO humanized mice","authors":"Yunmei Mu ,&nbsp;Yusuke Ohno ,&nbsp;Misa Mochizuki ,&nbsp;Kenji Kawai ,&nbsp;Motohito Goto ,&nbsp;Tomoyuki Ogura ,&nbsp;Riichi Takahashi ,&nbsp;Mamoru Ito ,&nbsp;Ryoji Ito","doi":"10.1016/j.imlet.2024.106943","DOIUrl":"10.1016/j.imlet.2024.106943","url":null,"abstract":"<div><div>Human immune system-reconstituted humanized mice are useful animal models to study human immunology <em>in vivo</em>. Human hematopoietic stem cell-transferred NOG mice are well recognized as humanized immune system models with reconstitution of mature lymphoid lineage cells such as T and B cells. However, human myeloid lineage cells including dendritic cells (DCs) do not fully differentiate in conventional NOG mice. DCs play a crucial role in adaptive immunity through antigen presentation to T cells to acquire antigen specificity. In this study, we established a novel humanized mouse with human DC differentiation. To induce DCs, we generated human Fms-like tyrosine kinase 3 ligand (hFLT3L) transgenic NOG (hFLT3L-Tg) mice and transferred human CD34⁺ hematopoietic stem cells (HSC) into them. Unexpectedly, low frequency of human cell engraftment was observed in the hFLT3L-Tg mice after HPC reconstitution. In the Tg mice, mouse CD11b⁺Gr1⁻ myeloid cells were markedly expanded in the bone marrow due to the cross-reaction between hFLT3L and mouse Flt3 receptor, and these myeloid leukemia-like cells interfered with the engraftment of human hematopoietic cells in hFLT3L-Tg mice. To avoid this cross-reaction, we further generated NOG FLT3 receptor KO (mFlt3 KO) mice by CRISPR/Cas9 technique, and the KO mice combined with hFLT3L Tg mice to create hFLT3L Tg/mFlt3 KO (FL Tg/KO) mice. Mouse CD11b⁺Gr1⁻ leukemia-like cells did not proliferate in FL Tg/KO mice due to blockade of the FLT3 signals in mouse leukocytes. After human HSC transplantation, human CD45⁺ cells were successfully engrafted in FL Tg/KO mice. Furthermore, major subsets of human DC populations, cDC1, cDC2, and pDC, and skin Langerhans cells were significantly differentiated in FL Tg/KO mice. Therefore, these humanized mouse models are potentially valuable in the investigation of DC-mediated human adaptive immune responses <em>in vivo</em>.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"270 ","pages":"Article 106943"},"PeriodicalIF":3.3,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rescuing pathogen-specific memory B-cell from PBMC of prior Zika virus-infected individuals","authors":"Jacyelle Medeiros Silva ,&nbsp;Renato Kaylan Alves de Oliveira França ,&nbsp;Pedro Henrique Barros ,&nbsp;Hitallo Guilherme Costa Fontinele ,&nbsp;Simone Gonçalves Fonseca ,&nbsp;Marcelo Macedo Brigido ,&nbsp;Andrea Queiroz Maranhão","doi":"10.1016/j.imlet.2024.106944","DOIUrl":"10.1016/j.imlet.2024.106944","url":null,"abstract":"<div><div>Immunological memory, a fundamental immune system mechanism, is instrumental in long-term protection. Successful vaccines can elicit and sustain immunological memory against pathogens for the long term. Memory B cells (MBC) are key players in secondary responses due to their longevity and rapid differentiation into high-affinity antibody-secreting cells upon second antigen exposure. However, the availability of circulating MBCs is limited. Here we describe a protocol, which presents a straightforward and practical method for activating and expanding Zika virus (ZIKV) specific MBC. PBMCs collected from individuals who had been infected with ZIKV two years prior were cultured by supplementing with IL-2 and R848, a TLR-7/8 agonist, and then pulsed with inactivated virus. After seven days, this stimulation led to a notable rise in virus-specific functional MBC, as evidenced by a significant increase in the production of anti-ZIKV IgG. Importantly, the ZIKV pulse did not induce changes in the PBMC culture of individuals without a history of ZIKV infection. These findings demonstrate that virus-specific MBC can be expanded <em>in vitro</em>, even using PBMC cultures from individuals infected years before. Therefore, our protocol is a practical and effective tool for studies that require a larger number of human MBCs from previously infected individuals that are functional and specific to the pathogen under investigation.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"271 ","pages":"Article 106944"},"PeriodicalIF":3.3,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eosinophils are sparse in homeostatic rectal tissue which impedes studying resident eosinophils","authors":"Thomas C. Pelgrim ,&nbsp;Bernard N. Jukema ,&nbsp;Nienke Vrisekoop,&nbsp;Leo Koenderman","doi":"10.1016/j.imlet.2024.106939","DOIUrl":"10.1016/j.imlet.2024.106939","url":null,"abstract":"","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"270 ","pages":"Article 106939"},"PeriodicalIF":3.3,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142604269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term monocyte activation after coronary artery bypass grafting: An exploratory prospective observational study","authors":"Wieteke Broeders ,&nbsp;Julia van Tuijl ,&nbsp;Harmke B. Duindam ,&nbsp;Annemieke M. Peters van Ton ,&nbsp;Marlies P. Noz ,&nbsp;Peter Pickkers ,&nbsp;Wilson F. Abdo ,&nbsp;Mihai G. Netea ,&nbsp;Siroon Bekkering ,&nbsp;Niels P. Riksen","doi":"10.1016/j.imlet.2024.106941","DOIUrl":"10.1016/j.imlet.2024.106941","url":null,"abstract":"<div><div>Major surgery such as coronary artery bypass grafting (CABG) is associated with an increased post-operative risk of atherosclerotic cardiovascular events. Cells of the innate immune system can adopt a long-lasting pro-inflammatory and atherogenic phenotype after brief exposure to exogenous or endogenous inflammatory stimuli, a process called “trained immunity”. We hypothesized that the surgery-induced inflammation leads to sustained alterations in monocyte function, which promote the subsequent occurrence of cardiovascular events. Blood from 13 patients undergoing elective CABG was obtained before, 3–7 days (median 4) after, and 6–8 weeks (median 6) weeks after surgery. At 3–7 days postoperatively, circulating C-reactive protein (CRP) concentration, leukocyte counts and <em>ex vivo</em> Peripheral Blood Mononuclear Cell (PBMC) IL-6, TNFα and IL-1Ra production after stimulation (with various inflammatory stimuli) were significantly increased. Simultaneously, there was a reduction in monocyte HLA-DR expression. 6–8 weeks after CABG there was an ongoing systemic pro-inflammatory state with higher CRP concentrations, increased stimulated <em>ex vivo</em> PBMC IL-6 production, changes in monocytes subsets, and a higher expression of CCR2 on monocytes compared to baseline. In conclusion, CABG induces a persistent systemic inflammatory reaction with a sustained activated monocyte phenotype. This might contribute to the increased atherosclerotic cardiovascular event risk observed in cardiac surgery patients.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"270 ","pages":"Article 106941"},"PeriodicalIF":3.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568200","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":"T cell landscape in the microenvironment of human solid tumors","authors":"Enrico Maggi ,&nbsp;Enrico Munari ,&nbsp;Nadine Landolina ,&nbsp;Francesca Romana Mariotti ,&nbsp;Bruno Azzarone ,&nbsp;Lorenzo Moretta","doi":"10.1016/j.imlet.2024.106942","DOIUrl":"10.1016/j.imlet.2024.106942","url":null,"abstract":"<div><div>T cells are the main effectors involved in anti-tumor immunity, mediating most of the adaptive response towards cancer. After priming in lymph nodes, tumor antigens-specific naïve T lymphocytes proliferate and differentiate into effector CD4+ and CD8+ T cells that migrate from periphery into tumor sites aiming to eliminate cancer cells. Then while most effector T cells die, a small fraction persists and recirculates as long-lived memory T cells which generate enhanced immune responses when re-encountering the same antigen. A number of T (and non-T) cell subsets, stably resides in non-lymphoid peripheral tissues and may provide rapid immune response independently of T cells recruited from blood, against the reemergence of cancer cells. When tumor grows, however, tumor cells have evaded immune surveillance of effector cells (NK and CTL cells) which are exhausted, thus favoring the local expansion of T (and non-T) regulatory cells.</div><div>In this review, the current knowledge of features of T cells present in the tumor microenvironment (TME) of solid adult and pediatric tumors, the mechanisms upregulating immune-checkpoint molecules and transcriptional and epigenetic landscapes leading to dysfunction and exhaustion of T effector cells are reviewed. The interaction of T cells with cancer- or TME non-neoplastic cells and their secreted molecules shape the T cell profile compromising the intrinsic plasticity of T cells and, therefore, favoring immune evasion. In this phase regulatory T cells contribute to maintain a high immunosuppressive TME thus facilitating tumor cell proliferation and metastatic spread. Despite the advancements of cancer immunotherapy, many tumors are unresponsive to immune checkpoint inhibitors, or therapeutical vaccines or CAR T cell-based adoptive therapy: some novel strategies to improve these T cell-based treatments are lastly proposed.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"270 ","pages":"Article 106942"},"PeriodicalIF":3.3,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of abnormal lipid metabolism on immunosenescence of the colonic lamina propria in mice of different ages","authors":"Fangyuan Cong ,&nbsp;Yang Zhang ,&nbsp;Jun Xu ,&nbsp;Xiaohui Fang ,&nbsp;Xia Li ,&nbsp;Qian Xue ,&nbsp;Jingtong Wang ,&nbsp;Yulan Liu","doi":"10.1016/j.imlet.2024.106940","DOIUrl":"10.1016/j.imlet.2024.106940","url":null,"abstract":"<div><div>Immunosenescence is an age-associated change in immunological function. The intestinal mucosal immune system is considered the largest immune system in the human body, and its immunosenescence is closely related to the occurrence and development of many diseases. In recent years, studies have identified a crucial correlation between abnormal lipid metabolism induced by high-fat diet (HFD) and immunity, but the effect and mechanism of HFD on colonic mucosal immunosenescence are still unclear. In this study, we established an abnormal lipid metabolism model at different ages by feeding male wild-type mice HFD and compared the immunosenescence of the spleen, which reflects systemic immunity, and the colonic lamina propria (LP), which reflects local immunity. The results showed that HFD could lead to abnormal lipid metabolism at different ages, accelerate systemic and local immunosenescence, and increase the expression of inflammatory factors in colonic tissue. The levels of abnormal biochemical indicators induced by HFD were closely related to the proportions of T cell subsets associated with immunosenescence. Overall, the results showed that HFD had the most significant impact on aged mice. This study provides new ideas for further understanding the relationship between abnormal lipid metabolism and intestinal mucosal immunosenescence.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"270 ","pages":"Article 106940"},"PeriodicalIF":3.3,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Could tolerance to DNA be broken in the gut in systemic lupus erythematosus?","authors":"Jo Spencer ,&nbsp;Sahil Jain","doi":"10.1016/j.imlet.2024.106937","DOIUrl":"10.1016/j.imlet.2024.106937","url":null,"abstract":"<div><div>The bacteria in the human colon outnumber the total number of nucleated cells in the human body by approximately 10:1. The DNA that the bacteria contain is enriched around 20-fold in immune stimulatory CpG motifs compared to the DNA of host cells. In addition, this DNA can have alternative more immunogeneic DNA structures and it may be presented to the immune system alongside other proinflammatory bacterial innate ligands such as LPS. To ensure that this immunostimulatory combination is not pathogenic, the luminal boundary of host tissues in the human gastrointestinal tract is protected by cells secreting bactericides together with the secreted enzyme DNASE1L3 that can break down bacterial DNA. Cells with RNA encoding DNASE1L3 are particularly abundant in the gut-associated lymphoid tissue where bacteria are specifically sampled into the body, alongside B cells noted for their T independent function. Importantly, individuals with loss of function mutations in DNASE1L3 develop anti-DNA antibodies and lupus symptoms.</div><div>In this review, we explore the possibility that a perfect storm might break tolerance to DNA: when bacterial DNA from microbiota that is not digested by DNASE1L3 directly encounters B cells that are not necessarily restricted by T cell dependence.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"270 ","pages":"Article 106937"},"PeriodicalIF":3.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560884","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":"The importance of type I interferon in orchestrating the cytotoxic T-cell response to cancer","authors":"Julia Busselaar ,&nbsp;Merel Sijbranda ,&nbsp;Jannie Borst","doi":"10.1016/j.imlet.2024.106938","DOIUrl":"10.1016/j.imlet.2024.106938","url":null,"abstract":"<div><div>Both type I interferon (IFN-I) and CD4⁺ T-cell help are required to generate effective CD8⁺ T-cell responses to cancer. We here outline based on existing literature how IFN-I signaling and CD4⁺ T-cell help are connected. Both impact on the functional state of dendritic cells (DCs), particularly conventional (c)DC1. The cDC1s are critical for crosspresentation of cell-associated antigens and for delivery of CD4⁺ T-cell help for cytotoxic T-lymphocyte (CTL) effector and memory differentiation. In infection, production of IFN-I is prompted by pathogen-associated molecular patterns (PAMPs), while in cancer it relies on danger-associated molecular patterns (DAMPs). IFN-I production by tumor cells and pDCs in the tumor micro-environment (TME) is often limited. IFN-I signals increase the ability of migratory cDC1s and cDC2s to transport tumor antigens to tumor-draining lymph nodes (tdLNs). IFN-I also enables cDC1s to form and sustain the platform for help delivery by stimulating the production of chemokines that attract CD4⁺ and CD8⁺ T cells. IFN-I promotes delivery of help in concert with CD40 signals by additive and synergistic impact on cross-presentation and provision of critical costimulatory and cytokine signals for CTL effector and memory differentiation. The scenario of CD4⁺ T-cell help therefore depends on IFN-I signaling. This scenario can play out in tdLNs as well as in the TME, thereby contributing to the cancer immunity cycle. The collective observations may explain why both IFN-I and CD4⁺ T-cell help signatures in the TME correlate with good prognosis and response to PD-1 targeting immunotherapy in human cancer. They also may explain why a variety of tumor types in which IFN-I signaling is attenuated, remain devoid of functional CTLs.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"270 ","pages":"Article 106938"},"PeriodicalIF":3.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study of the mechanism of fibroblast-like synoviocytes-derived exosomes inducing macrophages M1 polarization and CD8+T cells immune regulation ferroptosis and autophagy in rheumatoid arthritis","authors":"Fang Fang ,&nbsp;Mengqing Hua ,&nbsp;GenMing Yu","doi":"10.1016/j.imlet.2024.106936","DOIUrl":"10.1016/j.imlet.2024.106936","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects the joints. The pathogenesis of RA is complex, involving membrane lipid antioxidant systems, oxidative stress, and lipid peroxidation. In this study, it was found that cysteine dioxygenase 1 (CDO1) is significantly upregulated in RA fibroblast-like synoviocytes (RA-FLS) and that exosomes derived from these RA-FLS deliver CDO1 to promote M1 polarization of macrophages, thus facilitating RA progression. In the immune microenvironment, CD8⁺<em>T</em> cells play a role in immune regulation by producing cytokines such as interferon gamma (IFNγ) in various diseases. The results of this study suggested that in RA-FLS, CD8⁺<em>T</em> cells deliver IFNγ, which not only inhibits the viability of RA-FLS but also affects glutathione (GSH) through CDO1, regulating the GPX4 antioxidant signaling pathway to promote ferroptosis and autophagy in cells. It was also discovered that IFNγ enhances the expression of TRI69, ubiquitinates and degrades FSP1, thereby forming a cooperative regulation process of GPX4 and FSP1 in ferroptosis. These findings provide a new direction for the treatment of RA.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"270 ","pages":"Article 106936"},"PeriodicalIF":3.3,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fingolimod, an antagonist of sphingosine 1-phosphate, ameliorates Sjögren's syndrome by reducing the number of STAT3–induced germinal center B cells and increasing the number of Breg cells","authors":"Yeon Su Lee ,&nbsp;JooYeon Jhun ,&nbsp;Jeong Won Choi ,&nbsp;Sun-Hee Hwang ,&nbsp;Jin Seok Woo ,&nbsp;Kun Hee Lee ,&nbsp;Seung Cheon Yang ,&nbsp;A. Ram Lee ,&nbsp;Mi-La Cho","doi":"10.1016/j.imlet.2024.106935","DOIUrl":"10.1016/j.imlet.2024.106935","url":null,"abstract":"<div><h3>Background</h3><div>Sjögren's syndrome (SS) is an autoimmune disease caused by infiltrating lymphocytes. FTY720 affects the S1P signaling pathway, which plays a role in T and B cell migration from secondary lymphoid tissues to target organs. In this study, we investigate the regulatory mechanism of FTY720 in the context of SS.</div></div><div><h3>Method</h3><div>FTY720 was given orally every day to NOD mice. The salivary flow rate (SFR) and blood glucose level were assayed every 3 weeks. Histopathological features were investigated at the end of the study. In vitro, FTY720 was added to mouse splenocytes, and changes in the lymphocyte subsets were assessed.</div></div><div><h3>Results</h3><div>In vivo, FTY720 increased the SFR and reduced the blood glucose level. The salivary gland histological score and infiltration of the salivary glands by B and T cells were dramatically decreased. Furthermore, STAT expression in the salivary gland was decreased. In vitro, FTY720 inhibited Th17 cells, while increasing regulatory T (Treg) cells, respectively. Also, FTY720 decreased and increased the numbers of germinal center (GC) B cells and regulatory B cells (Breg cells), respectively. FTY720 decreased the IgG level in culture supernatants. Also, STAT3 activation was decreased by FTY720.</div></div><div><h3>Conclusion</h3><div>Our results show the therapeutic potential of FTY720 in the context of SS; FTY720 prevents lymphocyte migration from secondary lymphoid organs to target organs.</div></div>","PeriodicalId":13413,"journal":{"name":"Immunology letters","volume":"270 ","pages":"Article 106935"},"PeriodicalIF":3.3,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}