Article
Immunology
Seul Hye Ryu, Hyun Soo Shin, Hye Hyeon Eum, Ji Soo Park, Wanho Choi, Hye Young Na, Hyunju In, Tae-Gyun Kim, Sejung Park, Soomin Hwang, Moah Sohn, Eun-Do Kim, Kyoung Yul Seo, Hae-Ock Lee, Min-Geol Lee, Min Kyung Chu, Chae Gyu Park
Summary: Dendritic cells (DCs) play a crucial role in initiating adaptive immunity. Injecting granulocyte macrophage-colony stimulating factor (GM-CSF) can generate a distinct subset of DCs called GMiDCs in the spleen, which have superior antigen-presenting ability and can activate CD4(+) T cells and polarize Th2 cells. The generation of GMiDCs depends on the expression of GM-CSF receptor, and they can also be found in other tissues and during chronic allergic inflammation. This study provides important insights into the development and immune regulation of DCs.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Pailin Chiaranunt, Kyle Burrows, Louis Ngai, Siu Ling Tai, Eric Y. Y. Cao, Helen Liang, Homaira Hamidzada, Anthony Wong, Julia Gschwend, Pascal Fluchter, Meggie Kuypers, Tijana Despot, Abdul Momen, Sung Min Lim, Thierry Mallevaey, Christoph Schneider, Tyrrell Conway, Hiromi Imamura, Slava Epelman, Arthur Mortha
Summary: Maintaining macrophage heterogeneity is critical for intestinal tissue homeostasis and defense. This study reveals that microbial biochemical energy metabolism promotes CSF2 production by ILC3s in SILTs, which leads to the development of SAMs. CSF2 regulates the function of SAMs and contributes to antimicrobial defense. These findings highlight the importance of SILTs and CSF2-producing ILC3s in intestinal macrophage development and functional programming.
SCIENCE IMMUNOLOGY
(2023)
Article
Immunology
Qianyue Zhang, Qiaoling Song, Shan Liu, Yuting Xu, Danling Gao, Peizhe Lu, Yuantao Liu, Guanghui Zhao, Lihong Wu, Chenyang Zhao, Jinbo Yang
Summary: This study investigated the metabolic differences between GM-BMDMs and M-BMDMs and their consistency with protein levels through transcriptome and metabolome analysis. The core metabolic pathways of macrophages were found to be closely associated with canonical macrophage functions such as inflammatory response and phagocytosis.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, Research & Experimental
Adam L. Burrack, Zoe C. Schmiechen, Michael T. Patterson, Ebony A. Miller, Ellen J. Spartz, Meagan R. Rollins, Jackson F. Raynor, Jason S. Mitchell, Tsuneyasu Kaisho, Brian T. Fife, Ingunn M. Stromnes
Summary: We investigated the differential impact of myeloid subsets on immunity to pancreatic ductal adenocarcinoma (PDA). Our study demonstrates that tumor antigenicity shapes the composition and functionality of myeloid cells. The therapeutic effectiveness of adoptive T cell therapy or programmed cell death ligand 1 blockade relies on the presence of type 1 dendritic cells (cDC1), which support the survival and function of antitumor T cells. Our research highlights the essential role of cDC1s in sustaining effective antitumor T cells and reveals differential roles for cDC1s and monocytes/macrophages in guiding T cell fate and immunotherapy response.
Article
Medicine, General & Internal
Annette D. D. Wagner, Ulrike Wittkop, Jessica Thalmann, Tina Willmen, Vega Goedecke, Justyna Hodam, Simon Ronicke, Martin Zenke
Summary: In patients with GCA, glucocorticoid therapy leads to a rapid reduction in the number of DCs, an increase in apoptotic cells, and a decrease in the expression of mediators for cell migration. These findings suggest GM-CSF as a potential therapeutic target for GCA.
FRONTIERS IN MEDICINE
(2021)
Article
Oncology
Tatiana Smirnova, Caroline Spertini, Olivier Spertini
Summary: The interaction between macrophages and leukemia cells plays a crucial role in promoting leukemia cell survival and resistance to therapy. Inhibiting the CSF1 receptor can reprogram macrophage polarization, increase leukemia cell apoptosis, and improve sensitivity to treatment. Targeting the microenvironment, specifically macrophages and the CSF1 receptor, may be a novel approach for acute myeloid leukemia therapy to address issues of relapse.
Article
Immunology
Hyunju In, Ji Soo Park, Hyun Soo Shin, Seul Hye Ryu, Moah Sohn, Wanho Choi, Sejung Park, Soomin Hwang, Jeyun Park, Lihua Che, Tae-Gyun Kim, Min Kyung Chu, Hye Young Na, Chae Gyu Park
Summary: DCs can be generated from mouse bone marrow with GM-CSF or FLT3L treatment, and can be classified into different subsets based on marker expression and antibody staining. In FLT3L-treated cultures, a majority of cDC2-gated CD11c(+)MHCII(hi) cells exhibited a specific phenotype, suggesting a new cDC precursor population.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Gastroenterology & Hepatology
Arthur Mortha, Romain Remark, Diane Marie Del Valle, Ling-Shiang Chuang, Zhi Chai, Ines Alves, Catarina Azevedo, Joana Gaifem, Jerome Martin, Francesca Petralia, Kevin Tuballes, Vanessa Barcessat, Siu Ling Tai, Hsin-Hui Huang, Ilaria Laface, Yeray Arteaga Jerez, Gilles Boschetti, Nicole Villaverde, Mona D. Wang, Ujunwa M. Korie, Joseph Murray, Rok-Seon Choung, Takahiro Sato, Renee M. Laird, Scott Plevy, Adeeb Rahman, Joana Torres, Chad Porter, Mark S. Riddle, Ephraim Kenigsberg, Salome S. Pinho, Judy H. Cho, Miriam Merad, Jean-Frederic Colombel, Sacha Gnjatic
Summary: This study found that anti-granulocyte macrophage-colony stimulating factor autoantibodies (aGMAbs) can predict the diagnosis of complicated Crohn's disease (CD) long before the actual diagnosis. These antibodies recognize uniquely glycosylated epitopes, and their presence is associated with impaired immune balance and altered myeloid cell and innate lymphoid cell function.
Review
Immunology
Yingzi Chen, Fan Li, Mengqing Hua, Meng Liang, Chuanwang Song
Summary: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic growth factor that induces the differentiation of bone marrow progenitor cells into granulocytes and macrophages. However, it is now known that GM-CSF has multiple origins and pleiotropic effects. GM-CSF activates JAK2 and induces nuclear signals through JAK-STAT, MAPK, PI3K, and other pathways. GM-CSF plays a crucial role in interstitial lung disease, allergic lung disease, alcoholic lung disease, and pulmonary infections caused by bacteria, fungi, and viruses. This article reviews the latest understanding of the relationship between GM-CSF and lung homeostasis and diseases, highlighting the broader functions of GM-CSF beyond its name suggests.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Torki Alothaimeen, Evan Trus, Sameh Basta, Katrina Gee
Summary: The study reveals differences in macrophage development and cytokine expression between M-CSF and GM-CSF cells after virus infection. While R848-induced cytokine expression is enhanced, signaling molecule activation is decreased in LCMV-infected macrophages. Interestingly, TLR7 expression is maintained at higher levels in M-CSF cells compared to GM-CSF.
JOURNAL OF GENERAL VIROLOGY
(2021)
Article
Multidisciplinary Sciences
Juan Pablo Arnoletti, Joseph Reza, Armando Rosales, Alberto Monreal, Na'im Fanaian, Suzanne Whisner, Milan Srivastava, Julia Rivera-Otero, Gongxin Yu, Otto Phanstiel, Deborah A. Altomare, Quang Tran, Sally A. Litherland
Summary: PDAC CTCs have the potential to influence myeloid differentiation and/or antigen presenting cell activation in the PDAC portal blood microenvironment. Disrupting the interactions between CTCs and M-FBs may be a potential target for reversing the immunosuppression supporting CTC survival in the portal blood.
Article
Multidisciplinary Sciences
Xiu Teng, Li-Ping Li, Meng Tang, Hui-Fang Li, Xiang-Yi Ren, Ling Jiao, Sha-Sha Wu, Da-Chao Mou, Zhi-Yong Miao
Summary: This study induced a novel T cell subset called Th-GM cells in a mouse CHS model and found that they were mainly expanded at the site of injury and draining lymph nodes. This method can be used to further investigate the biology of Th-GM cells and explore therapeutic strategies centered on GM-CSF in various conditions.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2022)
Article
Biochemistry & Molecular Biology
Javiera Villar, Lea Ouaknin, Adeline Cros, Elodie Segura
Summary: During inflammation, monocytes can differentiate into either macrophages or dendritic cells. This study used single-cell RNA sequencing and computational analysis to identify different pathways of differentiation for these two cell types. It also identified key transcription factors involved in monocyte fate commitment.
Article
Medicine, Research & Experimental
Nardhy Gomez-Lopez, Valeria Garcia-Flores, Peck Yin Chin, Holly M. Groome, Melanie T. Bijland, Kerrilyn R. Diener, Roberto Romero, Sarah A. Robertson
Summary: Macrophages play a critical homeostatic regulatory role in late gestation and are implicated as a determinant of susceptibility to spontaneous preterm birth and fetal inflammatory injury.
Article
Cell Biology
Peter Deak, Bradley Studnitzer, Trevor Ung, Rachel Steinhardt, Melody Swartz, Aaron Esser-Kahn
Summary: In this study, a distinctive subpopulation of dendritic cells (DCs) that respond to pathogen-associated molecular patterns (PAMPs) was isolated and characterized. These cells, known as first responders (FRs), show increased responses to PAMPs and play a role in facilitating adaptive immune responses. Furthermore, they can be selectively targeted by vaccines to modulate antibody and T cell responses in vivo.
Article
Immunology
Yifan Zhan, Nancy Wang, Ajithkumar Vasanthakumar, Yuxia Zhang, Michael Chopin, Stephen L. Nutt, Axel Kallies, Andrew M. Lew
CELLULAR & MOLECULAR IMMUNOLOGY
(2020)
Article
Immunology
Junyun Lai, Sherly Mardiana, Imran G. House, Kevin Sek, Melissa A. Henderson, Lauren Giuffrida, Amanda X. Y. Chen, Kirsten L. Todd, Emma Petley, Jack D. Chan, Emma M. Carrington, Andrew M. Lew, Benjamin J. Solomon, Joseph A. Trapani, Katherine Kedzierska, Maximilien Evrard, Stephin J. Vervoort, Jason Waithman, Phillip K. Darcy, Paul A. Beavis
Article
Pharmacology & Pharmacy
Xiaoyan Liu, Zhe Li, Shuai Liu, Jing Sun, Zhanghua Chen, Min Jiang, Qingling Zhang, Yinghua Wei, Xin Wang, Yi-You Huang, Yinyi Shi, Yanhui Xu, Huifang Xian, Fan Bai, Changxing Ou, Bei Xiong, Andrew M. Lew, Jun Cui, Rongli Fang, Hui Huang, Jincun Zhao, Xuechuan Hong, Yuxia Zhang, Fuling Zhou, Hai-Bin Luo
ACTA PHARMACEUTICA SINICA B
(2020)
Article
Allergy
Lingli Zhou, Tao Liu, Bing Huang, Man Luo, Zhanghua Chen, Zhiyao Zhao, Jun Wang, Daniel Leung, Xingtian Yang, Koon Wing Chan, Yukun Liu, Liya Xiong, Peiyu Chen, Hongli Wang, Liping Ye, Hanquan Liang, Seth L. Masters, Andrew M. Lew, Sitang Gong, Fan Bai, Jing Yang, Pamela Pui-Wah Lee, Wanling Yang, Yan Zhang, Yu-Lung Lau, Lanlan Geng, Yuxia Zhang, Jun Cui
Summary: A rare NLRP3 variant was identified in 3 patients with gastrointestinal symptoms, which increased NLRP3 inflammasome activation and pyroptosis in macrophages. In a dextran sulfate sodium-induced acute colitis model, the variant in hematopoietic cells resulted in more severe colitis.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jun Wang, Yanhui Xu, Zhanghua Chen, Jiankun Liang, Zefeng Lin, Huiying Liang, Yiping Xu, Qi Wu, Xuanjie Guo, Junli Nie, Bingtai Lu, Bing Huang, Huifang Xian, Xiaohui Wang, Qiang Wu, Jixiao Zeng, Chengwei Chai, Meixue Zhang, Yuzhen Lin, Li Zhang, Shanmeizi Zhao, Yanlu Tong, Liang Zeng, Xiaoqiong Gu, Zhuang-gui Chen, Shuhong Yi, Tong Zhang, David Delfouneso, Yan Zhang, Stephen L. Nutt, Andrew M. Lew, Liwei Lu, Fan Bai, Huimin Xia, Zhe Wen, Yuxia Zhang
Article
Immunology
Shengbo Zhang, Hannah D. Coughlan, Mitra Ashayeripanah, Simona Seizova, Andrew J. Kueh, Daniel Brown, Wang Cao, Nicolas Jacquelot, Angela D'Amico, Andrew M. Lew, Yifan Zhan, Christopher J. Tonkin, Jose A. Villadangos, Gordon K. Smyth, Michael Chopin, Stephen L. Nutt
Summary: The transcription factor DC-SCRIPT plays a critical role in the development and function of conventional dendritic cells (cDC1), with its deficiency leading to impaired antigen capture and presentation capabilities. This study highlights the importance of DC-SCRIPT in maintaining the identity and functional attributes of cDC1s.
SCIENCE IMMUNOLOGY
(2021)
Article
Immunology
Yifan Zhan, Yuxia Zhang, Shengbo Zhang, Hannah Coughlan, Pedro L. Baldoni, Nicolas Jacquelot, Wang H. J. Cao, Simon Preston, Cynthia Louis, Jai Rautela, Marc Pellegrini, Ian P. Wicks, Warren S. Alexander, Leonard C. Harrison, Andrew M. Lew, Gordon K. Smyth, Stephen L. Nutt, Michael Chopin
Summary: The study found that selectively deleting core components of PRC2, either EZH2 or SUZ12, in CD11c-expressing myeloid cells had different effects on H3K27me3. While EZH2 deficiency did not affect the deposition and maintenance of H3K27me3 in DCs or hinder DC/macrophage homeostasis, SUZ12 deficiency significantly impacted the ability of DCs and macrophages to maintain H3K27me3. This suggests fundamentally different homeostatic mechanisms for tissue-resident myeloid cells versus DCs.
SCIENCE IMMUNOLOGY
(2021)
Article
Hematology
Emma M. Carrington, Cynthia Louis, Tobias Kratina, Manuela Hancock, Christine R. Keenan, Nadia Iannarella, Rhys S. Allan, Ahmad Z. Wardak, Peter E. Czabotar, Marco J. Herold, Robyn L. Schenk, Christine A. White, Damian D'Silva, Yuyan Yang, Wesley Wong, Huon Wong, Vanessa L. Bryant, Nicholas D. Huntington, Jai Rautela, Robyn M. Sutherland, Yifan Zhan, Jacinta Hansen, Duong Nhu, Guillaume Lessene, Ian P. Wicks, Andrew M. Lew
Summary: The study highlights the essential role of BCL-XL in maintaining neutrophils within inflammatory sites and demonstrates the therapeutic potential of BCL-XL inhibition in treating inflammatory diseases. The selective BCL-XL inhibitor reduces inflammatory neutrophil numbers and ameliorates tissue pathology in mouse models, indicating a promising approach for neutrophil-mediated diseases.
Article
Immunology
Li Sun, Wenjie Zhang, Lin Zhao, Yanfang Zhao, Fengge Wang, Andrew M. Lew, Yuekang Xu
Summary: The correlation between infections and vascular autoinflammatory diseases has long been recognized, but the immunological basis of healthy vasculatures that predispose to subsequent vascular autoimmunity during inflammation is not well characterized. This study investigated the immune cells in healthy vascular tissues and found a comprehensive set of immune cells with a higher proportion of innate components. Systemic inflammation eroded the immunotolerant state of vascular tissues, leading to upregulation of proinflammatory cytokines and enhanced antigen presentation by vascular dendritic cells (DCs), ultimately leading to vascular destruction. Different vascular DC subsets had selective effects, with monocyte-derived DCs being potent cytokine producers and B-cell activators, and conventional DCs, particularly cDC1, being efficient at presenting antigens to stimulate T cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Wayne J. Hawthorne, Evelyn J. Salvaris, Yi Vee Chew, Heather Burns, Joanne Hawkes, Helen Barlow, Min Hu, Andrew M. Lew, Mark B. Nottle, Philip J. O'Connell, Peter J. Cowan
Summary: Genetically modified pig donors, combined with immunosuppression, can provide long-term cure and excellent graft survival in diabetic baboon models.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Timothy Patton, Zhe Zhao, Xin Yi Lim, Eleanor Eddy, Huimeng Wang, Adam G. Nelson, Bronte Ennis, Sidonia B. G. Eckle, Michael N. T. Souter, Troi J. Pediongco, Hui-Fern Koay, Jian-Guo Zhang, Tirta M. Djajawi, Cynthia Louis, Najoua Lalaoui, Nicolas Jacquelot, Andrew M. Lew, Daniel G. Pellicci, James McCluskey, Yifan Zhan, Zhenjun Chen, Kate E. Lawlor, Alexandra J. Corbett
Summary: Cell death mechanisms in T lymphocytes vary depending on their developmental stage, cell subset, and activation status. However, the cell death control mechanisms of mucosal-associated invariant T (MAIT) cells, a specialized T cell population, are not well understood. In this study, it was found that MAIT cells express high levels of key necroptotic machinery, RIPK3 and MLKL proteins. Surprisingly, the loss of RIPK3, but not MLKL or caspase-8, specifically increased the abundance of MAIT cells in various organs, indicating a cell-intrinsic regulation of MAIT cell accumulation by RIPK3 signaling.
CELL DEATH & DISEASE
(2023)
Article
Immunology
Shengbo Zhang, Jai Rautela, Naiara G. Bediaga, Tatiana B. Kolesnik, Yue You, Junli Nie, Laura F. Dagley, Justin Bedo, Hanqing Wang, Li Sun, Robyn Sutherland, Elliot Surgenor, Nadia Iannarella, Rhys Allan, Fernando Souza-Fonseca-Guimaraes, Yi Xie, Qike Wang, Yuxia Zhang, Yuekang Xu, Stephen L. Nutt, Andrew M. Lew, Nicholas D. Huntington, Sandra E. Nicholson, Michael Chopin, Yifan Zhan
Summary: The cytokine GM-CSF can differentiate monocytes into macrophages with opposing functions, proinflammatory M1-like and immunosuppressive M2-like. In this study, it was found that the protein CIS plays a critical role in the GM-CSF signaling pathway, and deficiency of CIS leads to the differentiation of monocytes into immunosuppressive M2-like macrophages, promoting allergic inflammation.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Meeting Abstract
Immunology
Annabell Bachem, Christina Makhlouf, Katrina J. Binger, David P. de Souza, Dedreia Tull, Andrew M. Lew, Carolina Perdomo, Andreas Kupz, William Figgett, Fabienne Mackay, Moshe Oleshansky, Brendan E. Russ, Ian A. Parish, Axel Kallies, Malcolm McConville, Stephen J. Turner, Thomas Gebhardt, Sammy Bedoui
JOURNAL OF IMMUNOLOGY
(2020)