International immunology最新文献_第9页

The skin barrier and microbiome in infantile atopic dermatitis development: can skincare prevent onset? 婴儿特应性皮炎发育过程中的皮肤屏障和微生物群：皮肤护理能预防发病吗？

IF 4.8 4区医学

International immunology Pub Date : 2024-10-26 DOI: 10.1093/intimm/dxae038

Tomoka Ito, Yuumi Nakamura

{"title":"The skin barrier and microbiome in infantile atopic dermatitis development: can skincare prevent onset?","authors":"Tomoka Ito, Yuumi Nakamura","doi":"10.1093/intimm/dxae038","DOIUrl":"10.1093/intimm/dxae038","url":null,"abstract":"Atopic dermatitis (AD), a prevalent Th2-dominant skin disease, involves complex genetic and environmental factors, including mutations in the Filaggrin gene and dysbiosis of skin microbiota characterized by an increased abundance of Staphylococcus aureus. Our recent findings emphasize the pivotal role of the skin barrier's integrity and microbial composition in infantile AD and allergic diseases. Early skin dysbiosis predisposes infants to AD, suggesting targeted skincare practices as a preventive strategy. The effects of skincare interventions, particularly the application of moisturizers with the appropriate molar concentration of ceramides, cholesterol, and fatty acids, play a crucial role in restoring the skin barrier. Notably, our study revealed that appropriate skincare can reduce Streptococcus abundance while supporting Cutibacterium acnes presence, thus directly linking skincare practices to microbial modulation in neonatal skin. Despite the mixed outcomes of previous Randomized Controlled Trials on the efficacy of moisturizers in AD prevention, our research points to the potential of skincare intervention as a primary preventive method against AD by minimizing the impact of genetic and environmental factors. Furthermore, our research supports the notion that early aggressive management of eczema may reduce the incidence of food allergies, highlighting the necessity for multifaceted prevention strategies that address both the skin barrier and immune sensitization. By focusing on repairing the skin barrier and adjusting the skin's microbiome from birth, we propose a novel perspective on preventing infantile AD and allergic diseases, opening new avenues for future studies, and practices in allergy prevention.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"579-584"},"PeriodicalIF":4.8,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418844","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}

引用次数: 0

Dysfunction of type 1 and type 2 immune cells: a lesson from exhausted-like ILC2s and their activation-induced cell death. 1 型和 2 型免疫细胞的功能失调：从枯竭样 ILC2 及其活化诱导的细胞死亡中汲取教训。

IF 4.8 4区医学

International immunology Pub Date : 2024-10-26 DOI: 10.1093/intimm/dxae032

Takashi Ebihara, Toshiki Yamada, Akane Fuchimukai, Shunsuke Takasuga, Tentaro Endo, Takechiyo Yamada, Megumi Tatematsu

{"title":"Dysfunction of type 1 and type 2 immune cells: a lesson from exhausted-like ILC2s and their activation-induced cell death.","authors":"Takashi Ebihara, Toshiki Yamada, Akane Fuchimukai, Shunsuke Takasuga, Tentaro Endo, Takechiyo Yamada, Megumi Tatematsu","doi":"10.1093/intimm/dxae032","DOIUrl":"10.1093/intimm/dxae032","url":null,"abstract":"The concept of immune cell exhaustion/dysfunction has developed mainly to understand impaired type 1 immune responses, especially by CD8 T-cells against tumors or virus-infected cells, and has been applied to other lymphocytes. Natural killer (NK) cells and CD4 T cells support the efficient activation of CD8 T cells but exhibit dysfunctional phenotypes in tumor microenvironments and in chronic viral infections. In contrast, the concept of type 2 immune cell exhaustion/dysfunction is poorly established. Group 2 innate lymphoid cells (ILC2s) and T-helper 2 (Th2) cells are the major lymphocyte subsets that initiate and expand type 2 immune responses for antiparasitic immunity or allergy. In mouse models of chronic parasitic worm infections, Th2 cells display impaired type 2 immune responses. Chronic airway allergy induces exhausted-like ILC2s that quickly fall into activation-induced cell death to suppress exaggerated inflammation. Thus, the modes of exhaustion/dysfunction are quite diverse and rely on the types of inflammation and the cells. In this review, we summarize current knowledge of lymphocyte exhaustion/dysfunction in the context of type 1 and type 2 immune responses and discuss ILC2-specific regulatory mechanisms during chronic allergy.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"585-594"},"PeriodicalIF":4.8,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11511622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093264","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}

引用次数: 0

The role of the skin in the atopic march. 皮肤在特应性进展中的作用。

IF 4.4 4区医学

International immunology Pub Date : 2024-09-13 DOI: 10.1093/intimm/dxae053

Xin Tang,Mei Li

引用次数: 0

Regnase-1 D141N mutation induces CD4+ T cell-mediated lung granuloma formation via upregulation of Pim2. Regnase-1 D141N突变通过上调Pim2诱导CD4+ T细胞介导的肺肉芽肿形成。

IF 4.8 4区医学

International immunology Pub Date : 2024-09-10 DOI: 10.1093/intimm/dxae026

Thin Sandi Htun, Hiroki Tanaka, Shailendra Kumar Singh, Diego Diez, Shizuo Akira

{"title":"Regnase-1 D141N mutation induces CD4+ T cell-mediated lung granuloma formation via upregulation of Pim2.","authors":"Thin Sandi Htun, Hiroki Tanaka, Shailendra Kumar Singh, Diego Diez, Shizuo Akira","doi":"10.1093/intimm/dxae026","DOIUrl":"10.1093/intimm/dxae026","url":null,"abstract":"Regnase-1 is an RNase that plays a critical role in negatively regulating immune responses by destabilizing inflammatory messenger RNAs (mRNAs). Dysfunction of Regnase-1 can be a major cause of various inflammatory diseases with tissue injury and immune cell infiltration into organs. This study focuses on the role of the RNase activity of Regnase-1 in developing inflammatory diseases. We have constructed mice with a single point mutation at the catalytic center of the Regnase-1 RNase domain, which lacks endonuclease activity. D141N mutant mice demonstrated systemic inflammation, immune cell infiltration into various organs, and progressive development of lung granuloma. CD4+ T cells, mainly affected by this mutation, upregulated the mTORC1 pathway and facilitated the autoimmune trait in the D141N mutation. Moreover, serine/threonine kinase Pim2 contributed to lung inflammation in this mutation. Inhibition of Pim2 kinase activity ameliorated granulomatous inflammation, immune cell infiltration, and proliferation in the lungs. Additionally, Pim2 inhibition reduced the expression of adhesion molecules on CD4+ T cells, suggesting a role for Pim2 in facilitating leukocyte adhesion and migration to inflamed tissues. Our findings provide new insights into the role of Regnase-1 RNase activity in controlling immune functions and underscore the therapeutic relevance of targeting Pim2 to modulate abnormal immune responses.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"497-516"},"PeriodicalIF":4.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140862153","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}

引用次数: 0

Humoral responses are enhanced by facilitating B cell viability by Fcrl5 overexpression in B cells. B 细胞中 Fcrl5 的过表达可促进 B 细胞的活力，从而增强体液反应。

IF 4.8 4区医学

International immunology Pub Date : 2024-09-10 DOI: 10.1093/intimm/dxae028

Chisato Ono, Yuta Kochi, Yoshihiro Baba, Shinya Tanaka

引用次数: 0

Lipid metabolism: a central modulator of RORγt-mediated Th17 cell differentiation. 脂质代谢：RORt 介导的 Th17 细胞分化的核心调节器。

IF 4.8 4区医学

International immunology Pub Date : 2024-09-10 DOI: 10.1093/intimm/dxae031

Toshio Kanno, Keisuke Miyako, Yusuke Endo

{"title":"Lipid metabolism: a central modulator of RORγt-mediated Th17 cell differentiation.","authors":"Toshio Kanno, Keisuke Miyako, Yusuke Endo","doi":"10.1093/intimm/dxae031","DOIUrl":"10.1093/intimm/dxae031","url":null,"abstract":"Among the T helper cell subsets, Th17 cells contribute to the development of various inflammatory and autoimmune diseases, including psoriasis, rheumatoid arthritis, inflammatory bowel disease, steroid-resistant asthma, and multiple sclerosis. Retinoid-related orphan receptor gamma t (RORγt), a nuclear hormone receptor, serves as a master transcription factor for Th17 cell differentiation. Recent findings have shown that modulating the metabolic pathway is critical for Th17 cell differentiation, particularly through the engagement of de novo lipid biosynthesis. Suppression of lipid biosynthesis, either through the pharmacological inhibition or gene deletion of related enzymes in CD4+ T cells, results in significant impairment of Th17 cell differentiation. Mechanistic studies indicate that metabolic fluxes through both the fatty acid and cholesterol biosynthetic pathways have a pivotal role in the regulation of RORγt activity through the generation of endogenous RORγt lipid ligands. This review discusses recent discoveries highlighting the importance of lipid metabolism in Th17 cell differentiation and function, as well as exploring specific molecular pathways involved in RORγt activation through cellular lipid metabolism. We further elaborate on a pioneering therapeutic approach to improve inflammatory and autoimmune disorders via the inhibition of RORγt.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"487-496"},"PeriodicalIF":4.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186301","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}

引用次数: 0

Altering the competitive environment of B cell epitopes significantly extends the duration of antibody production. 改变 B 细胞表位的竞争环境可大大延长抗体的产生时间。

IF 4.8 4区医学

International immunology Pub Date : 2024-09-10 DOI: 10.1093/intimm/dxae027

Hongke Xu, Yanfei Chen, Jingzhi Li, Mengyu Li, Miao Sun, Jian Chen, Ling Li, Qinghong Xue, Hongwei Ma

{"title":"Altering the competitive environment of B cell epitopes significantly extends the duration of antibody production.","authors":"Hongke Xu, Yanfei Chen, Jingzhi Li, Mengyu Li, Miao Sun, Jian Chen, Ling Li, Qinghong Xue, Hongwei Ma","doi":"10.1093/intimm/dxae027","DOIUrl":"10.1093/intimm/dxae027","url":null,"abstract":"Persistent immunoglobulin G (IgG) production (PIP) provides long-term vaccine protection. While variations in the duration of protection have been observed with vaccines prepared from different pathogens, little is known about the factors that determine PIP. Here, we investigated the impact of three parameters on the duration of anti-peptide IgG production, namely amino acid sequences, protein carriers, and immunization programs. We show that anti-peptide IgG production can be transformed from transient IgG production (TIP) to PIP, by placing short peptides (Pi) containing linear B cell epitopes in different competitive environments using bovine serum albumin (BSA) conjugates instead of the original viral particles. When goats were immunized with the peste des petits ruminants (PPR) live-attenuated vaccine (containing Pi as the constitutive component) and BSA-Pi conjugate, anti-Pi IgG production exhibited TIP (duration < 60 days) and PIP (duration > 368 days), respectively. Further, this PIP was unaffected by subsequent immunization with the PPR live-attenuated vaccine in the same goat. When goats were coimmunized with PPR live-attenuated vaccine and BSA-Pi, the induced anti-Pi IgG production showed a slightly extended TIP (from ~60 days to ~100 days). This discovery provides new perspectives for studying the fate of plasma cells in humoral immune responses and developing peptide vaccines related to linear neutralizing epitopes from various viruses.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"517-528"},"PeriodicalIF":4.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857033","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}

引用次数: 0

Blockade of CCR5 and CXCR3 attenuates murine acute graft-versus-host disease through modulating donor-derived T-cell distribution and function. 通过调节供体源性 T 细胞的分布和功能，阻断 CCR5 和 CXCR3 可减轻小鼠急性移植物抗宿主疾病。

IF 4.8 4区医学

International immunology Pub Date : 2024-09-10 DOI: 10.1093/intimm/dxae033

Bo Tang, Chenchen Qin, Huihui Liu, Shengchao Miao, Chao Xue, Zhenhua Wang, Yang Zhang, Yujun Dong, Wei Liu, Hanyun Ren

{"title":"Blockade of CCR5 and CXCR3 attenuates murine acute graft-versus-host disease through modulating donor-derived T-cell distribution and function.","authors":"Bo Tang, Chenchen Qin, Huihui Liu, Shengchao Miao, Chao Xue, Zhenhua Wang, Yang Zhang, Yujun Dong, Wei Liu, Hanyun Ren","doi":"10.1093/intimm/dxae033","DOIUrl":"10.1093/intimm/dxae033","url":null,"abstract":"Lymphocyte trafficking via chemokine receptors such as C-C chemokine receptor 5 (CCR5) and CXCR3 plays a critical role in the pathogenesis of acute graft-versus-host disease (aGVHD). Our previous studies showed that the addition of CCR5 or CXCR3 antagonists could only slightly alleviate the development of aGVHD. Given the specificity of T lymphocytes bearing CXCR3 and CCR5, we investigated whether combined CCR5 and CXCR3 blockade could further attenuate murine aGVHD. A mouse model of aGVHD was established to assess the efficacy of CCR5 and/or CXCR3 blockade on the development of aGVHD. The distribution of lymphocytes was calculated by quantification of immunostaining cells. The immunomodulatory effect on T cells was assessed by evaluating T-cell proliferation, viability, and differentiation. Using the murine allogeneic hematopoietic stem cell transplantation model, we demonstrated that blockade of both CCR5 and CXCR3 could efficiently alleviate the development of aGVHD. Further investigation on the immune mechanisms for this prophylactic effect showed that more T cells were detained into secondary lymphoid organs (SLOs), which may lead to reduced infiltration of T cells into GVHD target organs. Our study also showed that T cells detained in SLOs dampened the activation, suppressed the polarization toward T helper type 1 (Th1) and T cytotoxic type 1 (Tc1) cells, and induced the production of Treg cells. These data suggest that concurrent blockade of CCR5 and CXCR3 attenuates murine aGVHD through modulating donor-derived T-cell distribution and function, and this might be applicable for aGVHD prophylaxis in clinical settings.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"541-552"},"PeriodicalIF":4.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11385202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081220","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}

引用次数: 0

Identification and characterization of putative enhancer regions that direct Il6 transcription in murine macrophages. 小鼠巨噬细胞中指导 Il6 转录的推定增强子区域的鉴定和特征描述

IF 4.8 4区医学

International immunology Pub Date : 2024-08-13 DOI: 10.1093/intimm/dxae024

Norisuke Kano, Takeo Miki, Yurina Uehara, Daisuke Ori, Taro Kawai

{"title":"Identification and characterization of putative enhancer regions that direct Il6 transcription in murine macrophages.","authors":"Norisuke Kano, Takeo Miki, Yurina Uehara, Daisuke Ori, Taro Kawai","doi":"10.1093/intimm/dxae024","DOIUrl":"10.1093/intimm/dxae024","url":null,"abstract":"Interleukin-6 (IL-6) plays a crucial role in various cellular functions, including innate and adaptive immune responses. Dysregulated expression of IL-6 is associated with hyperinflammation and chronic inflammatory diseases. In this study, we aimed to identify the enhancer regions responsible for robust Il6 mRNA expression in murine macrophages. Through comprehensive genome-wide ChIP- and ATAC-seq analyses, we identified two distinct clusters, termed E1 and E2 regions, located at -144 to -163 kb relative to the Il6 transcription start site in lipopolysaccharide (LPS)-activated murine macrophages. These clusters exhibited an accumulation of histone modification marks (H3K27ac and H3K4me1), as well as open chromatin, and were found to contain binding sites for the transcription factors PU.1, NF-κB, C/EBPβ, and JunB. Upregulation of non-coding RNA (ncRNA) transcripts from the E1 and E2 regions was observed upon LPS stimulation, and repression of these ncRNAs resulted in abrogation of Il6 expression. Additionally, deletion of either E1 or E2 region significantly impaired Il6 expression, while CRISPR/dCas9 activation-mediated recruitment of the co-activator p300 to the E1 and E2 regions facilitated Il6 expression. Collectively, our findings suggest that the E1 and E2 regions serve as putative enhancers for Il6 expression.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"471-481"},"PeriodicalIF":4.8,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140851224","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}

引用次数: 0

Identification of potential C1-binding sites in the immunoglobulin CL domains. 鉴定免疫球蛋白 CL 结构域中潜在的 C1 结合位点。

IF 4.8 4区医学

International immunology Pub Date : 2024-07-13 DOI: 10.1093/intimm/dxae017

Saeko Yanaka, Atsuji Kodama, Shigetaka Nishiguchi, Rina Fujita, Jiana Shen, Pornthip Boonsri, Duckyong Sung, Yukiko Isono, Hirokazu Yagi, Yohei Miyanoiri, Takayuki Uchihashi, Koichi Kato

{"title":"Identification of potential C1-binding sites in the immunoglobulin CL domains.","authors":"Saeko Yanaka, Atsuji Kodama, Shigetaka Nishiguchi, Rina Fujita, Jiana Shen, Pornthip Boonsri, Duckyong Sung, Yukiko Isono, Hirokazu Yagi, Yohei Miyanoiri, Takayuki Uchihashi, Koichi Kato","doi":"10.1093/intimm/dxae017","DOIUrl":"10.1093/intimm/dxae017","url":null,"abstract":"Immunoglobulin G (IgG) molecules that bind antigens on the membrane of target cells spontaneously form hexameric rings, thus recruiting C1 to initiate the complement pathway. However, our previous report indicated that a mouse IgG mutant lacking the Cγ1 domain activates the pathway independently of antigen presence through its monomeric interaction with C1q via the CL domain, as well as Fc. In this study, we investigated the potential interaction between C1q and human CL isoforms. Quantitative single-molecule observations using high-speed atomic force microscopy revealed that human Cκ exhibited comparable C1q binding capabilities with its mouse counterpart, surpassing the Cλ types, which have a higher isoelectric point than the Cκ domains. Nuclear magnetic resonance and mutation experiments indicated that the human and mouse Cκ domains share a common primary binding site for C1q, centred on Glu194, a residue conserved in the Cκ domains but absent in the Cλ domains. Additionally, the Cγ1 domain, with its high isoelectric point, can cause electrostatic repulsion to the C1q head and impede the C1q-interaction adjustability of the Cκ domain in Fab. The removal of the Cγ1 domain is considered to eliminate these factors and thus promote Cκ interaction with C1q with the potential risk of uncontrolled activation of the complement pathway in vivo in the absence of antigen. However, this research underscores the presence of potential subsites in Fab for C1q binding, offering promising targets for antibody engineering to refine therapeutic antibody design.","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"405-412"},"PeriodicalIF":4.8,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11245854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335484","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}

引用次数: 0