International immunology最新文献

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Decreased TAX1BP1 participates in systemic lupus erythematosus by regulating monocyte/macrophage function. TAX1BP1降低通过调节单核细胞/巨噬细胞功能参与系统性红斑狼疮。
IF 4.4 4区 医学
International immunology Pub Date : 2023-10-06 DOI: 10.1093/intimm/dxad027
Tian Qian, Bengang Huo, Xiaorong Deng, Xiaoli Song, Yiwei Jiang, Jurong Yang, Fei Hao
{"title":"Decreased TAX1BP1 participates in systemic lupus erythematosus by regulating monocyte/macrophage function.","authors":"Tian Qian,&nbsp;Bengang Huo,&nbsp;Xiaorong Deng,&nbsp;Xiaoli Song,&nbsp;Yiwei Jiang,&nbsp;Jurong Yang,&nbsp;Fei Hao","doi":"10.1093/intimm/dxad027","DOIUrl":"10.1093/intimm/dxad027","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) involves disorders of innate and adaptive immune pathways. Tax1-binding protein 1 (TAX1BP1) modulates the production of antibodies in B cells and the T-cell cycle by regulating the NF-κB signaling pathway. However, the potential association of TAX1BP1 with SLE and its role in monocytes/macrophages have not been fully elucidated. In this study, we utilized whole-exome sequencing (WES) in combination with Sanger sequencing and identified 16 gene mutations, including in TAX1BP1, in an SLE family. TAX1BP1 protein expression with western blotting detection was reduced in SLE patients and correlated with disease activity negatively. Furthermore, RNA sequencing and 4D Label-Free Phosphoproteomic analysis were employed to characterize the transcriptome and phosphoproteome profiles in THP-1 and THP-1-differentiated M1 macrophages with TAX1BP1 knockdown. Silencing of TAX1BP1 in THP-1 and THP-1-differentiated M1 macrophages led to an increase in cluster of differentiation 80 (CD80) expression and differential changes in CD14 and CD16 expression, as assessed by flow cytometry. Additionally, western blot analysis showed that knockdown of TAX1BP1 led to a reduction in TRAF6 and p-p65 in THP-1-differentiated macrophages, with or without lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-α stimulation. Taken together, our findings suggest that TAX1BP1 participates in SLE activity by regulating antigen presentation in monocytes and inflammatory responses in M1 macrophages.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"483-495"},"PeriodicalIF":4.4,"publicationDate":"2023-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9828927","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
NOTCH4 potentiates the IL-13 induced genetic program in M2 alternative macrophages through the AP1 and IRF4-JMJD3 axis. NOTCH4通过AP1和IRF4-JMJD3轴增强M2替代巨噬细胞中IL-13诱导的遗传程序。
IF 4.4 4区 医学
International immunology Pub Date : 2023-10-06 DOI: 10.1093/intimm/dxad028
Susana López-López, María José Romero de Ávila, María Julia González-Gómez, María Luisa Nueda, Victoriano Baladrón, Eva M Monsalve, José Javier García-Ramírez, María José M Díaz-Guerra
{"title":"NOTCH4 potentiates the IL-13 induced genetic program in M2 alternative macrophages through the AP1 and IRF4-JMJD3 axis.","authors":"Susana López-López,&nbsp;María José Romero de Ávila,&nbsp;María Julia González-Gómez,&nbsp;María Luisa Nueda,&nbsp;Victoriano Baladrón,&nbsp;Eva M Monsalve,&nbsp;José Javier García-Ramírez,&nbsp;María José M Díaz-Guerra","doi":"10.1093/intimm/dxad028","DOIUrl":"10.1093/intimm/dxad028","url":null,"abstract":"<p><p>IL-13 signaling polarizes macrophages to an M2 alternatively activated phenotype, which regulates tissue repair and anti-inflammatory responses. However, an excessive activation of this pathway leads to severe pathologies, such as allergic airway inflammation and asthma. In this work, we identified NOTCH4 receptor as an important modulator of M2 macrophage activation. We show that the expression of NOTCH4 is induced by IL-13, mediated by Janus kinases and AP1 activity, probably mediated by the IL-13Rα1 and IL-13Rα2 signaling pathway. Furthermore, we demonstrate an important role for NOTCH4 signaling in the IL-13 induced gene expression program in macrophages, including various genes that contribute to pathogenesis of the airways in asthma, such as ARG1, YM1, CCL24, IL-10, or CD-163. We also demonstrate that NOTCH4 signaling modulates IL-13-induced gene expression by increasing IRF4 activity, mediated, at least in part, by the expression of the histone H3K27me3 demethylase JMJD3, and by increasing AP1-dependent transcription. In summary, our results provide evidence for an important role of NOTCH4 signaling in alternative activation of macrophages by IL-13 and suggest that NOTCH4 may contribute to the increased severity of lesions in M2 inflammatory responses, such as allergic asthma, which points to NOTCH4 as a potential new target for the treatment of these pathologies.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"497-509"},"PeriodicalIF":4.4,"publicationDate":"2023-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9841270","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
The ligand interactions of B cell Siglecs are involved in the prevention of autoimmunity to sialylated self-antigens and in the quality control of signaling-competent B cells. B细胞Siglecs的配体相互作用涉及对唾液酸化自身抗原的自身免疫的预防和信号传导能力B细胞的质量控制。
IF 4.4 4区 医学
International immunology Pub Date : 2023-10-06 DOI: 10.1093/intimm/dxad030
Takeshi Tsubata
{"title":"The ligand interactions of B cell Siglecs are involved in the prevention of autoimmunity to sialylated self-antigens and in the quality control of signaling-competent B cells.","authors":"Takeshi Tsubata","doi":"10.1093/intimm/dxad030","DOIUrl":"10.1093/intimm/dxad030","url":null,"abstract":"<p><p>Sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of membrane molecules that recognize sialic acid. Most of them are inhibitory receptors that inhibit immune-cell activation by recognizing sialic acid as a self-motif. Human B cells express CD22 (also known as Siglec-2), Siglec-5, Siglec-6 and Siglec-10 whereas mouse B cells express CD22 and Siglec-G (ortholog of human Siglec-10). Siglecs recognize both sialylated molecules expressed on the same cell (cis-ligands) and those expressed by other cells (trans-ligands). In Guillain-Barré syndrome (GBS), antibody production to gangliosides (which are sialic acid-containing glycolipids) expressed by neurons plays a pathogenic role. A Siglec-10 variant deficient in recognition of gangliosides is genetically associated with GBS, suggesting that Siglec-10 induces self-tolerance to gangliosides by recognizing gangliosides as trans-ligands. Recognition of the BCR as a cis-ligand by Siglec-G and CD22 suppresses BCR signaling in B-1 cells and conventional B cells, respectively. This signal suppression prevents excess expansion of B-1 cells and is involved in the quality control of signaling-competent B cells by setting a threshold for tonic signaling during B cell development. CD22 recognizes other cis-ligands including CD22 and β7 integrin. Interaction of CD22 with other CD22 molecules induces CD22 clustering that suppresses CD22-mediated signal inhibition upon BCR ligation, and interaction with β7 integrin maintains its function in the gut-homing of B cells. Taken together, interactions of B cell Siglecs with multiple trans- and cis-ligands play important roles in B cell homeostasis and immune responses.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"461-473"},"PeriodicalIF":4.4,"publicationDate":"2023-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10260479","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
Low-dose perinatal supplementation with Enterococcus faecalis increases concentrations of short-chain fatty acids in the offspring but does not protect against allergic asthma. 低剂量围产期补充粪肠球菌会增加后代中短链脂肪酸的浓度,但不能预防过敏性哮喘。
IF 4.4 4区 医学
International immunology Pub Date : 2023-10-06 DOI: 10.1093/intimm/dxad025
Jeanne L Arntz, Moumen M Alhasan, Swarali Datye, Fariz G Kahhaleh, Yahia Almousa, Gabriela Barrientos, Andreas Schwiertz, Melanie L Conrad
{"title":"Low-dose perinatal supplementation with Enterococcus faecalis increases concentrations of short-chain fatty acids in the offspring but does not protect against allergic asthma.","authors":"Jeanne L Arntz,&nbsp;Moumen M Alhasan,&nbsp;Swarali Datye,&nbsp;Fariz G Kahhaleh,&nbsp;Yahia Almousa,&nbsp;Gabriela Barrientos,&nbsp;Andreas Schwiertz,&nbsp;Melanie L Conrad","doi":"10.1093/intimm/dxad025","DOIUrl":"10.1093/intimm/dxad025","url":null,"abstract":"<p><p>Childhood allergic asthma is associated with a dysbiotic gut microbiome in early life, and maternal perinatal treatment with probiotics is a potential way alter the infant microbiome, which may improve asthma outcomes. This study used a mouse model to examine the effect of maternal supplementation with the probiotic Enterococcus faecalis on faecal short-chain fatty acid (SCFA) concentrations and asthma risk in the offspring. Pregnant/lactating mice were treated daily, from gestation day 6 to postnatal day 21, with an oral suspension of 106, 107 or 108 colony-forming units of a live preparation of the probiotic E. faecalis (Symbioflor®1). At weaning, offspring were subjected to an ovalbumin-induced experimental asthma protocol. Faeces were collected from the mothers and offspring at several different time points to determine SCFA concentrations. It was found that maternal supplementation with E. faecalis did not alter litter size, sex ratio or offspring weight, and was associated with an increase in SCFAs in offspring faeces at weaning and after allergy induction. However, allergic offspring from E. faecalis supplemented mothers showed no difference in asthma severity when compared with allergic offspring from control mothers. In conclusion, although maternal perinatal supplementation with low-dose E. faecalis was associated with increased faecal SCFAs in the offspring, it did not protect against offspring asthma. This is may be because SCFA concentrations were not increased to an immunoprotective level. We recommend that future studies concentrate on probiotic supplementation in high-risk cases, for instance, to repair gut dysbiosis resulting from antibiotic use in pregnant mothers or their infants.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":"475-482"},"PeriodicalIF":4.4,"publicationDate":"2023-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9886807","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
Foxp3 and Bcl6 deficiency synergistically induces spontaneous development of atopic dermatitis-like skin disease. Foxp3和Bcl6缺乏协同诱导特应性皮炎样皮肤病的自发发展。
IF 4.4 4区 医学
International immunology Pub Date : 2023-09-05 DOI: 10.1093/intimm/dxad018
Yuki Tai, Yuki Sakaida, Riyo Kawasaki, Kaori Kanemaru, Kazunori Akimoto, Frank Brombacher, Shuhei Ogawa, Yoshikazu Nakamura, Yohsuke Harada
{"title":"Foxp3 and Bcl6 deficiency synergistically induces spontaneous development of atopic dermatitis-like skin disease.","authors":"Yuki Tai,&nbsp;Yuki Sakaida,&nbsp;Riyo Kawasaki,&nbsp;Kaori Kanemaru,&nbsp;Kazunori Akimoto,&nbsp;Frank Brombacher,&nbsp;Shuhei Ogawa,&nbsp;Yoshikazu Nakamura,&nbsp;Yohsuke Harada","doi":"10.1093/intimm/dxad018","DOIUrl":"https://doi.org/10.1093/intimm/dxad018","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is a common chronic skin disease caused by immune dysfunction, specifically the hyperactivation of Th2 immunity. AD is a complex disease with multiple factors contributing to its development; however, the interaction between these factors is not fully understood. In this study, we demonstrated that the conditional deletion of both the forkhead box p3 (Foxp3) and B-cell lymphoma 6 (Bcl6) genes induced the spontaneous development of AD-like skin inflammation with hyperactivation of type 2 immunity, skin barrier dysfunction, and pruritus, which were not induced by the single deletion of each gene. Furthermore, the development of AD-like skin inflammation was largely dependent on IL-4/13 signaling but not on immunoglobulin E (IgE). Interestingly, we found that the loss of Bcl6 alone increased the expression of thymic stromal lymphopoietin (TSLP) and interleukin (IL)-33 in the skin, suggesting that Bcl6 controls Th2 responses by suppressing TSLP and IL-33 expression in epithelial cells. Our results suggest that Foxp3 and Bcl6 cooperatively suppress the pathogenesis of AD. Furthermore, these results revealed an unexpected role of Bcl6 in suppressing Th2 responses in the skin.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":"35 9","pages":"423-435"},"PeriodicalIF":4.4,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10207602","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: 1
Contributions of the N-terminal flanking residues of an antigenic peptide from the Japanese cedar pollen allergen Cry j 1 to the T-cell activation by HLA-DP5. 杉木花粉过敏原cryj1抗原肽n端侧翼残基对HLA-DP5激活t细胞的贡献
IF 4.4 4区 医学
International immunology Pub Date : 2023-09-05 DOI: 10.1093/intimm/dxad024
Seisuke Kusano, Sho Ueda, Daisuke Oryoji, Aya Toyoumi, Akiko Hashimoto-Tane, Hiroyuki Kishi, Hiroshi Hamana, Atsushi Muraguchi, Hui Jin, Hisashi Arase, Hiroko Miyadera, Reiko Kishikawa, Yasunobu Yoshikai, Hisakata Yamada, Ken Yamamoto, Yasuharu Nishimura, Takashi Saito, Takehiko Sasazuki, Shigeyuki Yokoyama
{"title":"Contributions of the N-terminal flanking residues of an antigenic peptide from the Japanese cedar pollen allergen Cry j 1 to the T-cell activation by HLA-DP5.","authors":"Seisuke Kusano,&nbsp;Sho Ueda,&nbsp;Daisuke Oryoji,&nbsp;Aya Toyoumi,&nbsp;Akiko Hashimoto-Tane,&nbsp;Hiroyuki Kishi,&nbsp;Hiroshi Hamana,&nbsp;Atsushi Muraguchi,&nbsp;Hui Jin,&nbsp;Hisashi Arase,&nbsp;Hiroko Miyadera,&nbsp;Reiko Kishikawa,&nbsp;Yasunobu Yoshikai,&nbsp;Hisakata Yamada,&nbsp;Ken Yamamoto,&nbsp;Yasuharu Nishimura,&nbsp;Takashi Saito,&nbsp;Takehiko Sasazuki,&nbsp;Shigeyuki Yokoyama","doi":"10.1093/intimm/dxad024","DOIUrl":"https://doi.org/10.1093/intimm/dxad024","url":null,"abstract":"<p><p>Cry j 1 is a major allergen present in Japanese cedar (Cryptomeria japonica) pollens. Peptides with the core sequence of KVTVAFNQF from Cry j 1 ('pCj1') bind to HLA-DP5 and activate Th2 cells. In this study, we noticed that Ser and Lys at positions -2 and -3, respectively, in the N-terminal flanking (NF) region to pCj1 are conserved well in HLA-DP5-binding allergen peptides. A competitive binding assay showed that the double mutation of Ser(-2) and Lys(-3) to Glu [S(P-2)E/K(P-3)E] in a 13-residue Cry j 1 peptide (NF-pCj1) decreased its affinity for HLA-DP5 by about 2-fold. Similarly, this double mutation reduced, by about 2-fold, the amount of NF-pCj1 presented on the surface of mouse antigen-presenting dendritic cell line 1 (mDC1) cells stably expressing HLA-DP5. We established NF-pCj1-specific and HLA-DP5-restricted CD4+ T-cell clones from HLA-DP5 positive cedar pollinosis (CP) patients, and analyzed their IL-2 production due to the activation of mouse TG40 cells expressing the cloned T-cell receptor by the NF-pCj1-presenting mDC1 cells. The T-cell activation was actually decreased by the S(P-2)E/K(P-3)E mutation, corresponding to the reduction in the peptide presentation by this mutation. In contrast, the affinity of NF-pCj1·HLA-DP5 for the T-cell receptor was not affected by the S(P-2)E/K(P-3)E mutation, as analyzed by surface plasmon resonance. Considering the positional and side-chain differences of these NF residues from previously reported T-cell activating sequences, the mechanisms of enhanced T-cell activation by Ser(-2) and Lys(-3) of NF-pCj1 may be novel.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":"35 9","pages":"447-458"},"PeriodicalIF":4.4,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10478803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10205320","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
A CCR4 antagonist attenuates atopic dermatitis-like skin inflammation by inhibiting the recruitment and expansion of Th2 cells and Th17 cells. CCR4拮抗剂通过抑制Th2细胞和Th17细胞的募集和扩增来减轻特应性皮炎样皮肤炎症。
IF 4.4 4区 医学
International immunology Pub Date : 2023-09-05 DOI: 10.1093/intimm/dxad019
Masako Sato, Kazuhiko Matsuo, Yoko Susami, Ayaka Yamashita, Haruko Hayasaka, Yuta Hara, Keiji Nishiwaki, Naoki Oiso, Akira Kawada, Atsushi Otsuka, Takashi Nakayama
{"title":"A CCR4 antagonist attenuates atopic dermatitis-like skin inflammation by inhibiting the recruitment and expansion of Th2 cells and Th17 cells.","authors":"Masako Sato,&nbsp;Kazuhiko Matsuo,&nbsp;Yoko Susami,&nbsp;Ayaka Yamashita,&nbsp;Haruko Hayasaka,&nbsp;Yuta Hara,&nbsp;Keiji Nishiwaki,&nbsp;Naoki Oiso,&nbsp;Akira Kawada,&nbsp;Atsushi Otsuka,&nbsp;Takashi Nakayama","doi":"10.1093/intimm/dxad019","DOIUrl":"https://doi.org/10.1093/intimm/dxad019","url":null,"abstract":"<p><p>CCR4 is a major trafficking receptor for T-helper (Th) 2 cells and Th17 cells and is considered as a potential therapeutic target for atopic dermatitis (AD). The CCR4 ligands CCL17 and CCL22 have been reported to be upregulated in the skin lesions of AD patients. Of note, thymic stromal lymphopoietin (TSLP), a master regulator of the Th2 immune response, promotes the expression of CCL17 and CCL22 in AD skin lesions. Here, we investigated the role of CCR4 in an AD mouse model induced by MC903, a TSLP inducer. Topical application of MC903 to ear skin increased the expression of not only TSLP but also CCL17, CCL22, the Th2 cytokine IL-4, and the Th17 cytokine IL-17A. Consistently, MC903 induced AD-like skin lesions as shown by increased epidermal thickness; increased infiltration of eosinophils, mast cells, type 2 innate lymphoid cells, Th2 cells, and Th17 cells; and elevated serum levels of total IgE. We also found increased expansion of Th2 cells and Th17 cells in the regional lymph nodes (LNs) of AD mice. Compound 22, a CCR4 inhibitor, ameliorated AD-like skin lesions with reduction of Th2 cells and Th17 cells in the skin lesions and regional LNs. We further confirmed that compound 22 diminished the expansion of Th2 cells and Th17 cells in the coculture of CD11c+ dendritic cells (DCs) and CD4+ T cells derived from the regional LNs of AD mice. Collectively, CCR4 antagonists may exhibit anti-allergic effects by inhibiting both the recruitment and expansion of Th2 cells and Th17 cells in AD.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":"35 9","pages":"437-446"},"PeriodicalIF":4.4,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10209730","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
Computer model of IL-6-dependent rheumatoid arthritis in F759 mice. F759 小鼠 IL-6 依赖性类风湿性关节炎的计算机模型。
IF 4.4 4区 医学
International immunology Pub Date : 2023-09-05 DOI: 10.1093/intimm/dxad016
Reiji Yamamoto, Satoshi Yamada, Toru Atsumi, Kaoru Murakami, Ari Hashimoto, Seiichiro Naito, Yuki Tanaka, Izuru Ohki, Yuta Shinohara, Norimasa Iwasaki, Akihiko Yoshimura, Jing-Jing Jiang, Daisuke Kamimura, Shintaro Hojyo, Shimpei I Kubota, Shigeru Hashimoto, Masaaki Murakami
{"title":"Computer model of IL-6-dependent rheumatoid arthritis in F759 mice.","authors":"Reiji Yamamoto, Satoshi Yamada, Toru Atsumi, Kaoru Murakami, Ari Hashimoto, Seiichiro Naito, Yuki Tanaka, Izuru Ohki, Yuta Shinohara, Norimasa Iwasaki, Akihiko Yoshimura, Jing-Jing Jiang, Daisuke Kamimura, Shintaro Hojyo, Shimpei I Kubota, Shigeru Hashimoto, Masaaki Murakami","doi":"10.1093/intimm/dxad016","DOIUrl":"10.1093/intimm/dxad016","url":null,"abstract":"<p><p>The interleukin-6 (IL-6) amplifier, which describes the simultaneous activation of signal transducer and activator of transcription 3 (STAT3) and NF-κb nuclear factor kappa B (NF-κB), in synovial fibroblasts causes the infiltration of immune cells into the joints of F759 mice. The result is a disease that resembles human rheumatoid arthritis. However, the kinetics and regulatory mechanisms of how augmented transcriptional activation by STAT3 and NF-κB leads to F759 arthritis is unknown. We here show that the STAT3-NF-κB complex is present in the cytoplasm and nucleus and accumulates around NF-κB binding sites of the IL-6 promoter region and established a computer model that shows IL-6 and IL-17 (interleukin 17) signaling promotes the formation of the STAT3-NF-κB complex followed by its binding on promoter regions of NF-κB target genes to accelerate inflammatory responses, including the production of IL-6, epiregulin, and C-C motif chemokine ligand 2 (CCL2), phenotypes consistent with in vitro experiments. The binding also promoted cell growth in the synovium and the recruitment of T helper 17 (Th17) cells and macrophages in the joints. Anti-IL-6 blocking antibody treatment inhibited inflammatory responses even at the late phase, but anti-IL-17 and anti-TNFα antibodies did not. However, anti-IL-17 antibody at the early phase showed inhibitory effects, suggesting that the IL-6 amplifier is dependent on IL-6 and IL-17 stimulation at the early phase, but only on IL-6 at the late phase. These findings demonstrate the molecular mechanism of F759 arthritis can be recapitulated in silico and identify a possible therapeutic strategy for IL-6 amplifier-dependent chronic inflammatory diseases.</p>","PeriodicalId":13743,"journal":{"name":"International immunology","volume":"35 9","pages":"403-421"},"PeriodicalIF":4.4,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10573679","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
In This Issue 本期报道
IF 4.4 4区 医学
International immunology Pub Date : 2023-09-01 DOI: 10.1093/intimm/dxad026
{"title":"In This Issue","authors":"","doi":"10.1093/intimm/dxad026","DOIUrl":"https://doi.org/10.1093/intimm/dxad026","url":null,"abstract":"","PeriodicalId":13743,"journal":{"name":"International immunology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43340183","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
Subcutaneous immunisation with zymosan generates mucosal IgA-eliciting memory and protects mice from heterologous influenza virus infection. 用酶生酶皮下免疫产生粘膜iga诱导记忆并保护小鼠免受异源流感病毒感染。
IF 4.4 4区 医学
International immunology Pub Date : 2023-08-07 DOI: 10.1093/intimm/dxad013
Yoshihito Nihei, Mizuki Higashiyama, Kosuke Miyauchi, Kei Haniuda, Yusuke Suzuki, Masato Kubo, Daisuke Kitamura
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