IL-33 Deficiency Attenuates Lung Inflammation by Inducing Th17 Response and Impacting the Th17/Treg Balance in LPS-Induced ARDS Mice via Dendritic Cells by Li Cheng, Yang Jiao, Wei Jiang, Xin Zhang, Liping Zhang, Gongwei Jia

“…The levels of IL-33, orphan nuclear receptor gamma t (RORγt), and forkhead transcription factor protein 3 (FOXP3) protein in lung tissue were evaluated by Western blotting. …”
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Therapeutic Efficacy of <i>Lavandula dentata</i>’s Oil and Ethanol Extract in Regulation of the Neuroinflammation, Histopathological Alterations, Oxidative Stress, and Restoring Ba... by Aziza Antar, Eman S. Abdel-Rehiem, Areej A. Al-Khalaf, Abdelaziz S. A. Abuelsaad, Mohamed Abdel-Gabbar, Gaber M. G. Shehab, Ayman M. Abdel-Aziz

“…Moreover, <i>L. dentata’s</i> oil and ethanol extract re-balances T-reg/Th-17 cytokines, restoring the pro/anti-inflammatory cytokines and Treg markers, e.g., FOXP3 and CTLA-4, to their normal level. <b>Conclusions</b>: The present work confirms that the extract and essential oils of <i>L. dentata</i> L. have different activities to ameliorate the progression of histopathological alterations. …”
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Sequence-structure based prediction of pathogenicity for amino acid substitutions in proteins associated with primary immunodeficiencies by Ekaterina S. Porfireva, Anton D. Zadorozhny, Anastasia V. Rudik, Dmitry A. Filimonov, Alexey A. Lagunin, Alexey A. Lagunin

“…In this study, we have developed classification sequence-structure-property relationships (SSPR) models for predicting the pathogenicity of amino acid substitutions (AAS) in 25 proteins associated with the most important and genetically studied PIDs and encoded genes: IL2RG, JAK3, RAG1, RAG2, ADA, DCLRE1C, CD40LG, WAS, ATM, STAT3, KMT2D, BTK, FOXP3, AIRE, FAS, ELANE, ITGB2, CYBB, G6PD, GATA2, STAT1, IFIH1, NLRP3, MEFV, and SERPING1.MethodsThe data on 4825 pathogenic and benign AASs in the selected proteins were extracted from ClinVar and gnomAD. …”
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Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes in Advanced Melanoma Patients by Mélanie Saint-Jean, Anne-Chantal Knol, Christelle Volteau, Gaëlle Quéreux, Lucie Peuvrel, Anabelle Brocard, Marie-Christine Pandolfino, Soraya Saiagh, Jean-Michel Nguyen, Christophe Bedane, Nicole Basset-Seguin, Amir Khammari, Brigitte Dréno

“…Notably, patients treated with high percentages of CD4 + CD25 + CD127lowFoxp3+ T cells among their TILs had significantly shorter OS. …”
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Peripheral Regulatory Cells Immunophenotyping in Kidney Transplant Recipients with Different Clinical Profiles: A Cross-Sectional Study by Janette Furuzawa-Carballeda, Guadalupe Lima, Perla Simancas, Dolores Ramos-Bello, Margaret Simancas, Ian C. Bostock, Mario Vilatobá, Bernardo Gabilondo, Julio Granados, Luis Morales-Buenrostro, Josefina Alberú, Luis Llorente

“…Regulatory Foxp3-expressing T cells (Tregs), IL-10-producing B cells (Bregs), and IDO-expressing dendritic cells (DCregs) downregulate inflammatory processes and induces peripheral tolerance. …”
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Correlation and diagnostic significance of CD4 T cell subsets and NLRP3 inflammasome in ulcerative colitis: the role of the NLRP3/T-bet/GATA3 axis by Yingnan Hu, Jingyi Tang, Dian Yu, Shuo Su, Jintao Fang, Linying Xia, Wenjun Xu, Weihan Zhu, Ninping Song, Fengyong Wang, Dechang Diao, Wei Zhang

“…Additionally, Th1 and Th2 cytokines (IL-2 and IL-4) were significantly elevated in severe UC, while Treg markers (FOXP3, IL-10, TGF-β1) were elevated only in mild-to-moderate UC. …”
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Cysticerci Drive Dendritic Cells to Promote In Vitro and In Vivo Tregs Differentiation by Laura Adalid-Peralta, Asiel Arce-Sillas, Gladis Fragoso, Graciela Cárdenas, Marcos Rosetti, Didier Casanova-Hernández, Claudia Rangel-Escareño, Laura Uribe-Figueroa, Agnes Fleury, Edda Sciutto

“…Monocyte-derived dendritic cells (DC) from healthy human donors, cocultivated with autologous CD4+ naïve cells either in the presence or absence of cysticerci, promoted CD25highFoxp3+ Treg differentiation. An increased Treg induction was observed when cysticerci were present. …”
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Prognostic value of tumor‐infiltrating lymphocytes and PD‐L1 expression in esophageal squamous cell carcinoma by Jie Hu, Takeshi Toyozumi, Kentaro Murakami, Satoshi Endo, Yasunori Matsumoto, Ryota Otsuka, Tadashi Shiraishi, Shinichiro Iida, Hiroki Morishita, Tenshi Makiyama, Yuri Nishioka, Masaya Uesato, Koichi Hayano, Akira Nakano, Hisahiro Matsubara

“…Immunohistochemical analysis and multiplex immunofluorescence for CD4, CD8, CD25, FOXP3, and PD‐L1 in the tumor were used to identify multiple tumor‐infiltrating immune cells (TIIC), Tregs, and TC. …”
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The Role of Circulating Regulatory T Cell Levels on Subclinical Atherosclerosis and Cardiovascular Risk Factors in Women with Systemic Lupus Erythematosus by Mario García-Carrasco, Pamela Soto-Santillán, Claudia Mendoza-Pinto, Rebeca González-Ramírez, Ana Lidia López-Carmona, Pamela Munguía-Realpozo, Ivet Etchegaray-Morales, Socorro Méndez-Martínez, José Luis Gálvez-Romero, Aurelio López-Colombo, Alejandro Ruiz-Arguelles

“…Flow cytometry was used to analyze Foxp3 and Helios expression in peripheral blood CD4 T cells. …”
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Mechanistic investigation and the optimal dose based on baicalin in the treatment of ulcerative colitis–A preclinical systematic review and meta-analysis by Jinchen Chong, Zepeng Chen, Jiaze Ma, Linhai He, Yijia Zhu, Zhihua Lu, Zhengxi Qiu, Chen Chen, Yugen Chen, Feng Jiang

“…Baicalin significantly modulated various biomarkers: HCS (SMD = -3.91), DAI (MD = -2.75), spleen index (MD = -12.76), MDA (SMD = -3.88), IL-6 (SMD = -10.59), IL-1β (SMD = -3.98), TNF-α (SMD = -8.05), NF-κB (SMD = -5.46), TLR4 (MD = -0.38), RORγ (MD = -0.89), MCP-1 (MD = -153.25), MPO (SMD = -7.34), Caspase-9 (MD = -0.93), Caspase-3 (MD = -0.45), FasL (MD = -1.20)) and enhanced BWC (MD = 0.06), CL (MD = 1.39), ZO-1 (MD = 0.44), SOD (SMD = 3.04), IL-10 mRNA (MD = 3.14), and FOXP3 (MD = 0.45) levels. Baicalin’s actions may involve the PI3K/AKT, TLR4/NF-κB, IKK/IKB, Bcl-2/Bax, Th17/Treg, and TLRs/MyD88 pathways. …”
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Syngeneic natural killer cell therapy activates dendritic and T cells in metastatic lungs and effectively treats low-burden metastases by Shih-Wen Huang, Yein-Gei Lai, Hao-Ting Liao, Chin-Ling Chang, Ruo-Yu Ma, Yung-Hsiang Chen, Yae-Huei Liou, Zhen-Qi Wu, Yu-Chen Wu, Ko-Jiunn Liu, Yen-Tsung Huang, Jen-Lung Yang, Ming-Shen Dai, Nan-Shih Liao

“…Furthermore, NK cell transfer augments activation of conventional dendritic cells (cDCs), Foxp3-CD4+ T cells and stem cell-like CD8+ T cells in metastatic lungs, to which IFN-γ of the transferred NK cells contributes significantly. …”
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Cannabinoid receptor 2 selective agonist ameliorates adjuvant-induced arthritis by modulating the balance between Treg and Th17 cells by Na Tian, Cui Yang, Yu Du, Miao Chen, Bin Li, Bin Li, Bin Li, Bin Li, Bin Li, Dan Li, Sheng-Ming Dai

“…Western blot analysis indicated that HU-308 modulated immune balance through the JAK/STAT5 and TGF-β/SMAD signaling pathways, increasing Foxp3 and TGF-β expression.ConclusionHU-308 demonstrates significant anti-inflammatory effects in AIA by restoring Th17/Treg balance and reducing joint damage. …”
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MicroRNA Expression in Cutaneous Lupus: A New Window to Understand Its Pathogenesis by Silvia Méndez-Flores, Janette Furuzawa-Carballeda, Gabriela Hernández-Molina, Gustavo Ramírez-Martinez, Nora E. Regino-Zamarripa, Blanca Ortiz-Quintero, Luis Jiménez-Alvarez, Alfredo Cruz-Lagunas, Joaquín Zúñiga

“…Peripheral CD4+/CD25-/IL-4+ cells and CD4+/CD25hi/Foxp3+ were negatively associated with miR-23b, and CD4+/CD25-/IFN-γ+ with miR-1246 in SCLE, whereas CD123+/CD196+/IDO+ cells were positively associated with miR-150 in DLE. …”
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29 m6A-RNA Methylation (Epitranscriptomic) Regulators Are Regulated in 41 Diseases including Atherosclerosis and Tumors Potentially via ROS Regulation – 102 Transcriptomic Dataset... by Ming Liu, Keman Xu, Fatma Saaoud, Ying Shao, Ruijing Zhang, Yifan Lu, Yu Sun, Charles Drummer, Li Li, Sheng Wu, Satya P. Kunapuli, Gerard J. Criner, Jianxin Sun, Huimin Shan, Xiaohua Jiang, Hong Wang, Xiaofeng Yang

“…We performed a database mining on 102 transcriptomic datasets for the expressions of 29 m6A-RNA methylation (epitranscriptomic) regulators (m6A-RMRs) in 41 diseases and cancers and made significant findings: (1) a few m6A-RMRs were upregulated; and most m6A-RMRs were downregulated in sepsis, acute respiratory distress syndrome, shock, and trauma; (2) half of 29 m6A-RMRs were downregulated in atherosclerosis; (3) inflammatory bowel disease and rheumatoid arthritis modulated m6A-RMRs more than lupus and psoriasis; (4) some organ failures shared eight upregulated m6A-RMRs; end-stage renal failure (ESRF) downregulated 85% of m6A-RMRs; (5) Middle-East respiratory syndrome coronavirus infections modulated m6A-RMRs the most among viral infections; (6) proinflammatory oxPAPC modulated m6A-RMRs more than DAMP stimulation including LPS and oxLDL; (7) upregulated m6A-RMRs were more than downregulated m6A-RMRs in cancer types; five types of cancers upregulated ≥10 m6A-RMRs; (8) proinflammatory M1 macrophages upregulated seven m6A-RMRs; (9) 86% of m6A-RMRs were differentially expressed in the six clusters of CD4+Foxp3+ immunosuppressive Treg, and 8 out of 12 Treg signatures regulated m6A-RMRs; (10) immune checkpoint receptors TIM3, TIGIT, PD-L2, and CTLA4 modulated m6A-RMRs, and inhibition of CD40 upregulated m6A-RMRs; (11) cytokines and interferons modulated m6A-RMRs; (12) NF-κB and JAK/STAT pathways upregulated more than downregulated m6A-RMRs whereas TP53, PTEN, and APC did the opposite; (13) methionine-homocysteine-methyl cycle enzyme Mthfd1 downregulated more than upregulated m6A-RMRs; (14) m6A writer RBM15 and one m6A eraser FTO, H3K4 methyltransferase MLL1, and DNA methyltransferase, DNMT1, regulated m6A-RMRs; and (15) 40 out of 165 ROS regulators were modulated by m6A eraser FTO and two m6A writers METTL3 and WTAP. …”
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Dual-release hydrocortisone treatment improves serum and peripheral blood mononuclear cell inflammatory and immune profiles in patients with autoimmune primary adrenal insufficienc... by Laura Tomasello, Antonina Coppola, Giuseppe Pizzolanti, Giuseppe Pizzolanti, Carla Giordano, Giorgio Arnaldi, Valentina Guarnotta

“…Secondary outcomes included the evaluation of the CD4+CD25+Foxp3+ Treg population and the gene expression levels of IL-6, IL-17A, cyclooxygenase (COX)-2, heat shock proteins (HSP)-70, indoleamine-2,3-dioxygenase (IDO), programmed death-ligand 1 (PD-L1), inducible nitric oxide synthase (iNOS), and thioredoxin (TXN)-1.MethodsWe prospectively included 15 patients with PAI on conventional glucocorticoid (GC) replacement therapy, 15 switched to dual-release hydrocortisone (DR-HC), and 20 healthy controls. …”
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CD4 T cell dynamics shape the immune response to combination oncolytic herpes virus and BRAF inhibitor therapy for melanoma by Victoria Jennings, Kevin Harrington, Hardev Pandha, Alan Melcher, Adel Samson, Fiona Errington-Mais, Victoria Roulstone, Eva Crespo-Rodriguez, Galabina Bozhanova, Shane Foo, Emmanuel C Patin, Martin McLaughlin, Malin Pedersen, Richard Vile, Joan Kyula, Jehanne Hassan, Lizzie Appleton, Charleen ML Chan Wah Hak, Gabby Baker, Edward Armstrong, Matthew Chiu, Masahiro Ono

“…Transcriptomic analysis confirmed reduction in Foxp3 on addition of anti-CD25 to HSV/BRAFi, as well as increases in expression of genes reflecting interferon signaling and cytotoxic activity.Conclusions Combination HSV/BRAFi is an immunogenic therapy for BRAF mutant melanoma, but cannot fully control tumors. …”
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NPRL2 gene therapy induces effective antitumor immunity in KRAS/STK11 mutant anti-PD1 resistant metastatic non-small cell lung cancer (NSCLC) in a humanized mouse model by Ismail M Meraz, Mourad Majidi, Renduo Song, Feng Meng, Lihui Gao, Qi Wang, Jing Wang, Elizabeth J Shpall, Jack A Roth

“…IFNγ, CD8b, and TBX21 associated with T-cell functions were significantly increased, whereas FOXP3, TGFB1/B2, and IL-10RA were strongly inhibited by NPRL2. …”
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Correlation between immune signature and high‐density lipoprotein cholesterol level in stage II/III colorectal cancer by Yun Wang, Xiao‐qiang Sun, Hao‐cheng Lin, De‐shen Wang, Zhi‐qiang Wang, Qiong Shao, Feng‐hua Wang, Shu‐mei Yan, Jie‐ying Liang, Zhao‐lei Zeng, Huai‐qiang Ju, Rui‐hua Xu, Yu‐hong Li

“…Using immunohistochemistry, tumor tissues were stained with antibodies against CD3, CD8, CD163, iNOS, Forkhead box P3 (FOXP3), and CD33. We calculated the density of positively‐stained infiltrating cells in the tumor center (TC) and invasive margin (IM). …”
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Multiplex immunohistochemistry to explore the tumor immune microenvironment in HCC patients with different GPC3 expression by Mingzhen Zhou, Ziyan Zhou, Lina Hu, Sidong Chen, Fanyan Meng, Jun Chen, Jie Shen

“…Multiple immunohistochemical markers, such as CD8, PD-1, LAG3, TIGIT, TIM-3, CD103, Claudin18.2, PD-L1, CD4, Foxp3, CD68, CD163, GPC3, CD11C, CD14, CD66b, and HLA-DR, were used to characterize the immune microenvironment and spatial distribution of immune cells in HCC tumors with different levels of GPC3 expression. …”
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GDF15 induces immunosuppression via CD48 on regulatory T cells in hepatocellular carcinoma by Meng Li, Yuan Gao, Wei Zhang, Zhijun Tan, Kuo Zhang, Zhaowei Wang, Lei He, Weina Li, Chuanyang Xu, Jieyu Zhang, Desheng Wang, Kefeng Dou, Ran Zhuang, Boquan Jin, Qiang Hao, Wangqian Zhang, Shuning Wang, Jintao Gu, Lei Shang, Haichuan Su, Yingqi Zhang, Cun Zhang

“…GDF15 promotes the generation of peripherally derived inducible Treg (iTreg) cells and enhances the suppressive function of natural Treg (nTreg) cells by interacting with a previously unrecognized receptor CD48 on T cells and thus downregulates STUB1, an E3 ligase that mediates forkhead box P3 (FOXP3) protein degradation. GDF15 neutralizing antibody effectively eradicates HCC and augments the antitumor immunity in mouse.Conclusions Our results reveal the generation and function enhancement of Treg cells induced by GDF15 is a new mechanism for HCC-related immunosuppression. …”
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