Article
Allergy
Maryam Ghaedi, Fumio Takei
Summary: Innate lymphoid cells (ILCs) mainly reside at barrier surfaces and play a regulatory role in tissue homeostasis and immunity. They are divided into 3 groups based on similar effector programs to T cells, and their development from lymphoid progenitors in adult mouse bone marrow has been extensively studied.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Lily Chan, Yeganeh Mehrani, Jessica A. A. Minott, Byram W. W. Bridle, Khalil Karimi
Summary: Dendritic cell (DC) vaccines rely on the communication of DCs with other aspects of the immune system and have potential in immunotherapy. Innate lymphoid cells (ILCs) have important roles in health and disease. Studies using a murine model of DC-based vaccination showed changes in ILC3 populations after DC vaccine administration, particularly in the lungs upon challenge with melanoma cells. Further exploration of the interactions between DCs and ILC3s could have implications in health, disease, and the development of immunotherapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Y. F. van Lier, L. Krabbendam, N. J. E. Haverkate, S. S. Zeerleder, C. E. Rutten, B. Blom, H. Spits, M. D. Hazenberg
Summary: Innate lymphoid cells (ILCs) are important regulators of immune response in barrier tissues, playing roles in protection against pathogens, maintaining epithelial integrity, regulating immune responses, and shaping the gut microbiota. GATA2 haploinsufficiency, a condition characterized by bone marrow failure and deficiency of certain immune cells, results in the absence of ILCs and their progenitors. However, after allogeneic hematopoietic stem cell transplantation, all subsets of ILCs appear, suggesting the involvement of GATA2 in the development of hematopoietic precursor cells (HPC) towards the ILC lineage.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Kaitlin A. Read, Devin M. Jones, Aharon G. Freud, Kenneth J. Oestreich
Summary: Ikaros zinc finger transcription factors play important roles in lymphoid cell development, with nuanced and stage-specific effects on T, B, and innate lymphoid cell populations. Interacting both within and between family members, the precise transcriptional mechanisms of these factors, including their regulation of cytokine signaling, are actively being investigated.
IMMUNOLOGICAL REVIEWS
(2021)
Article
Chemistry, Multidisciplinary
Feng Li, Zhou Liang, Haojie Zhong, Xinrong Hu, Ziwen Tang, Changjian Zhu, Jiani Shen, Xu Han, Ruoni Lin, Ruilin Zheng, Ruihan Tang, Huajing Peng, Xunhua Zheng, Chengqiang Mo, Peisong Chen, Xin Wang, Qiong Wen, Jianbo Li, Xi Xia, Hongjian Ye, Yagui Qiu, Jianwen Yu, Dongying Fu, Jiaqi Liu, Rong Wang, Huixin Xie, Yun Guo, Xiaoyan Li, Jinjin Fan, Qinghua Liu, Haiping Mao, Wei Chen, Yi Zhou
Summary: In lupus nephritis (LN), gut-derived group 3 innate lymphoid cells (ILC3s) migrate from the small intestine to the kidney via the CXCR6/CXCL16 axis, contributing to the progression of LN, including spleen and lymph node enlargement, antibody production, and renal injury. In renal ectopic lymphoid structures (ELS), ILC3s induce B cell activation in a Delta-like1 (DLL1)/Notch-dependent manner, accompanied by up-regulation of Deltex1 and MAML1.
Review
Immunology
Minghui Li, Zehui Wang, Wei Jiang, Yihan Lu, Jun Zhang
Summary: Group 3 innate lymphoid cells (ILC3s) are a subset of lymphocytes found in the intestinal mucosa, playing a crucial role in maintaining intestinal immune homeostasis. They secrete cytokines such as IL-22 to eliminate luminal antigens, promote tissue repair, and regulate intestinal immunity. However, dysfunction of ILC3s can contribute to the development of various gut diseases. This review focuses on recent research advances and discoveries regarding the role of ILC3s in enteric infectious diseases, intestinal inflammation, and tumors, aiming to explore potential therapeutic targets.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Horticulture
Tingting Chen, Jing Peng, Meijie Li, Mengru Dou, Yan Lei, Yuejing Wang, Yan Xu
Summary: This study identified the full gene families of GATA transcription factors in grapes and investigated their expression patterns in response to hormones and downy mildew infection. The results showed that some VvGATA genes had higher expression levels after hormone treatments and were dramatically induced in the resistant cultivar after infection. However, these genes were repressed in the sensitive cultivar. Additionally, the transcription factor VvGATA27 was located in the nucleus and had transcriptional activity.
Article
Immunology
Shijiu Jiang, Yuqi Zheng, Bingjie Lv, Shaolin He, Wenling Yang, Boyuan Wang, Jin Zhou, Shangwei Liu, Dazhu Li, Jibin Lin
Summary: This study identified five subsets of innate lymphoid cells (ILCs) in the heart, including three new subclusters: ILCdc, ILC2b, and ILCt. The cellular composition, signaling pathways, and cell communication networks of ILC subclusters were revealed. The findings provide insights into the roles of ILC subclusters in myocardial ischemic diseases and potential treatment targets.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Microbiology
Anna A. A. Korchagina, Ekaterina Koroleva, Alexei V. V. Tumanov
Summary: Mucosal tissue homeostasis is regulated by innate lymphoid cells (ILCs) which can rapidly respond to environmental changes by producing effector cytokines. However, dysregulation of ILCs can lead to immunopathology. This review discusses recent advances in understanding the plasticity of ILCs in response to pathogens and the role of transcription factors, cytokines, tissue microenvironment, gut microbiota, and hypoxia in this process.
Review
Immunology
Difeng Fang, Ayanna Healy, Jinfang Zhu
Summary: CD4 T helper (Th) cell subsets and their innate counterparts innate lymphoid cell (ILC) subsets display similar effector cytokine-producing capabilities during immune responses. The differentiation, development, and functions of these lymphoid cell subsets are regulated by lineage-determining transcription factors (LDTFs). This review discusses the functions of cis-regulatory elements in inducing LDTF expression during Th cell differentiation and ILC development, as well as the upstream signals involved in LDTF induction in vitro and in vivo. The possible mechanisms and physiological importance of regulating LDTF dynamic expression during ILC development and activation are also explored.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Jan-Hendrik Schroeder, Katrin Meissl, Dominika Hromadova, Jonathan W. Lo, Joana F. Neves, Jane K. Howard, Helena Helmby, Nick Powell, Birgit Strobl, Graham M. Lord
Summary: T-bet deficient mice show an increase in ILC3 cellularity but do not have a greater risk of developing spontaneous colitis. T-bet appears to control the number of ILC3 cells, but does not drive a pathogenic role of ILC3 in mice with a conventional specific pathogen-free microbiota.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Endocrinology & Metabolism
Robert S. Viger, Karine de Mattos, Jacques J. Tremblay
Summary: Understanding how genes are turned on and off is crucial for the development and function of different cell types. Transcription factors, such as the GATA family, play essential roles in controlling gene expression in the male gonads, impacting testis development, fetal testis gene expression, testicular disease, and XY sex differentiation in humans.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Immunology
Dan Yang, Xinning Guo, Tingxuan Huang, Chuntao Liu
Summary: Innate lymphoid cells play a crucial role in maintaining mucosal homeostasis and protecting against pathogens, with ILC3s emerging as key mediators of mucosal protection and repair through producing IL-17 and IL-22. Further research is needed to understand the role of pulmonary ILC3s in respiratory infections and chronic pulmonary inflammatory diseases.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Immunology
Thuy T. Luu, Jonas Norskov Sondergaard, Lucia Pena-Perez, Shabnam Kharazi, Aleksandra Krstic, Stephan Meinke, Laurent Schmied, Nicolai Frengen, Yaser Heshmati, Marcin Kierczak, Thibault Bouderlique, Arnika Kathleen Wagner, Charlotte Gustafsson, Benedict J. Chambers, Adnane Achour, Claudia Kutter, Petter Hoglund, Robert Mansson, Nadir Kadri
Summary: FOXO1 and FOXO3 coordinately regulate essential developmental genes at multiple stages during murine NK cell and ILC lineage commitment through orchestrating distinct molecular mechanisms.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Hiroshi Yano, David Artis
Summary: The immune system and peripheral nervous system surveil vital organs through various sensory mechanisms. How these two sensory systems integrate signals to orchestrate host responses remains incomplete. Recent research has shown how neurotrophic factors and neuronally derived factors regulate the functions of innate lymphoid cells (ILCs), establishing the neuro-ILC axis as a crucial component of broader neuro-immune interactions. Neurons also express receptors for many cytokines produced by ILCs, suggesting bidirectional neuro-immune interactions in regulating tissue homeostasis and inflammation.
CURRENT OPINION IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Mingzhu Zheng, Jinfang Zhu
Summary: Innate lymphoid cells (ILCs) are a population of lymphoid cells that do not express T cell or B cell antigen-specific receptors. They play a protective role against pathogens mainly at mucosal sites. ILCs mimic the functions of CD4 T helper (Th) subsets and are involved in different immune responses by expressing specific cytokines and transcription factors. They have been found to be important in intestinal inflammation and related disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Difeng Fang, Kairong Cui, Yaqiang Cao, Mingzhu Zheng, Takeshi Kawabe, Gangqing Hu, Jaspal S. Khillan, Dan Li, Chao Zhong, Dragana Jankovic, Alan Sher, Keji Zhao, Jinfang Zhu
Summary: Adaptive CD4(+) T helper cells and innate lymphoid cells utilize distinct enhancer elements for the induction of T-bet, a critical transcription factor, during their differentiation. IL-18 induces T-bet expression in NK cells through the interaction between RUNX3 and Tbx21-CNS-3, while IL-12 induces T-bet expression in Th1 cells through the binding of STAT to Tbx21-CNS-12.
Article
Immunology
Takeshi Kawabe, Thomas Ciucci, Kwang Soon Kim, Shunichi Tayama, Akihisa Kawajiri, Takumi Suzuki, Riou Tanaka, Naoto Ishii, Dragana Jankovic, Jinfang Zhu, Jonathan Sprent, Remy Bosselut, Alan Sher
Summary: In this study, using single-cell RNA sequencing and flow cytometry, we identified distinct subsets within self-driven MP CD4(+) T lymphocytes and found that they differ from conventional foreign Ag-specific memory cells in marker expression and functional relevance.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Gang Ren, Binbin Lai, Christelle Harly, Songjoon Baek, Yi Ding, Mingzhu Zheng, Yaqiang Cao, Kairong Cui, Yu Yang, Jinfang Zhu, Gordon L. Hager, Avinash Bhandoola, Keji Zhao
Summary: The differentiation of innate lymphoid cells (ILCs) from hematopoietic stem cells requires the progression through several multipotent progenitor stages. This study shows that there are distinct accessible chromatin regions in all lymphoid progenitors (ALPs), early ILC precursors (EILPs), and ILC precursors (ILCPs). Single-cell MNase-seq analyses reveal that EILPs contain subpopulations epigenetically primed toward dendritic cell or ILC lineages. Key transcription factors TCF-1 and GATA3 are found to be indispensable for the epigenetic priming of lineage-defining sites for ILCs at the EILP stage.
Article
Immunology
Wen Chen, Shuangfeng Chen, Chenghua Yan, Yaguang Zhang, Ronghua Zhang, Min Chen, Shufen Zhong, Weiguo Fan, Songling Zhu, Danyan Zhang, Xiao Lu, Jia Zhang, Yuying Huang, Lin Zhu, Xuezhen Li, Dawei Lv, Yadong Fu, Houkun Iv, Zhiyang Ling, Liyan Ma, Hai Jiang, Gang Long, Jinfang Zhu, Dong Wu, Bin Wu, Bing Sun
Summary: Sun and colleagues demonstrate that the secretion of IL-33 after allergen exposure is mediated by stress granule assembly and the generation of a neo-form p40 fragment of gasdermin D. These findings provide insights into the molecular mechanisms of allergen-induced airway inflammation and offer potential targets for the treatment of allergic respiratory diseases.
Article
Immunology
Leon Friesen, Raymond Kostlan, Qingyang Liu, Hao Yu, Jinfang Zhu, Nicholas Lukacs, Chang H. Kim
Summary: IL-9 is mainly produced by specialized T cells, mast cells, and group 2 innate lymphoid cells, and it regulates immune responses, including anti-helminth and allergic responses. In this study, the transcription factor GFI1 was found to have a negative role in the polarization of mouse Th9 cells, and its expression is controlled by liganded RARa.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Cell Biology
Rama K. Gurram, Danping Wei, Qiao Yu, Matthew J. Butcher, Xi Chen, Kairong Cui, Gangqing Hu, Mingzhu Zheng, Xiaoliang Zhu, Jangsuk Oh, Bing Sun, Joseph F. Urban Jr, Keji Zhao, Warren J. Leonard, Jinfang Zhu
Summary: Type 2 T helper (Th2) cells and group 2 innate lymphoid cells (ILC2s) play a protective role in helminth infection and allergies, but their importance and interaction in type 2 immune responses are still debated.
Review
Immunology
Difeng Fang, Ayanna Healy, Jinfang Zhu
Summary: CD4 T helper (Th) cell subsets and their innate counterparts innate lymphoid cell (ILC) subsets display similar effector cytokine-producing capabilities during immune responses. The differentiation, development, and functions of these lymphoid cell subsets are regulated by lineage-determining transcription factors (LDTFs). This review discusses the functions of cis-regulatory elements in inducing LDTF expression during Th cell differentiation and ILC development, as well as the upstream signals involved in LDTF induction in vitro and in vivo. The possible mechanisms and physiological importance of regulating LDTF dynamic expression during ILC development and activation are also explored.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Kairong Cui, Zuojia Chen, Yaqiang Cao, Shuai Liu, Gang Ren, Gangqing Hu, Difeng Fang, Danping Wei, Chengyu Liu, Jinfang Zhu, Chuan Wu, Keji Zhao
Summary: Interferon-y (IFN-y) is a key cytokine in response to viral or intracellular bacterial infection in mammals. A silencer (CNS-28) for the Ifng gene has been identified, which maintains Ifng silence by diminishing enhancer-promoter interactions within Ifng locus in a GATA3-dependent but T-bet-independent manner. CNS-28 plays a role in restraining Ifng transcription in NK cells, CD4+ cells, and CD8+ T cells, and its deficiency results in repressed type 2 immune responses and a shift in Th1 and Th2 paradigm.
Article
Immunology
Aran Son, Francoise Meylan, Julio Gomez-Rodriguez, Zenia Kaul, McKella Sylvester, Guido H. Falduto, Estefania Vazquez, Tamara Haque, Moses M. Kitakule, Chujun Wang, Kalpana Manthiram, Chen-Feng Qi, Jun Cheng, Rama K. Gurram, Jinfang Zhu, Pamela Schwartzberg, Joshua D. Milner, Pamela A. Frischmeyer-Guerrerio, Daniella M. Schwartz
Summary: Schwartz and colleagues found that T(H)9 cells can induce the expression of IL-9 independently through bystander activation by IL-2 and IL-4, promoting allergic inflammation. Targeting the STAT5/STAT6 activation cascade may provide relief for chronic allergy patients. Allergic diseases are a global health issue, and T(H)9 cells play a role in promoting allergic inflammation, but their exact mechanisms are not fully understood.
Article
Multidisciplinary Sciences
Luni Hu, Mengwei Han, Yichen Deng, Jingjing Gong, Zhiyuan Hou, Yanyu Zeng, Yime Zhang, Jing He, Chao Zhong
Summary: Through transcriptome comparison, two genesets capable of efficiently distinguishing tissue-residential natural killer (trNK) cells from conventional NK (cNK) cells have been defined. The activation of trNK and cNK shows a fundamental difference, with chromatin landscape and cytokine milieu playing important roles. IL-21 is critical in promoting trNK activation. This study expands our knowledge about the distinct functionalities of trNK and cNK during immune responses.
Article
Immunology
Yuanyuan Gao, Yan Wang, Daniel Chauss, Alejandro V. Villarino, Verena M. Link, Hiroyuki Nagashima, Camille A. Spinner, Vishal N. Koparde, Nicolas Bouladoux, Michael S. Abers, Timothy J. Break, Laura B. Chopp, Jung-Hyun Park, Jinfang Zhu, David L. Wiest, Warren J. Leonard, Michail S. Lionakis, John J. O'Shea, Behdad Afzali, Yasmine Belkaid, Vanja Lazarevic
Summary: Lazarevic and colleagues demonstrate that the transcription factor EGR2 controls a pathogenic T(H)17 cell-specific transcriptional program in the CNS. EGR2 is elevated in myelin-reactive CD4(+) T cells from patients with multiple sclerosis and mice with autoimmune neuroinflammation. Mechanistically, EGR2 enhances T(H)17 cell differentiation and myeloid cell recruitment to the CNS by upregulating pathogenesis-associated genes and myelomonocytic chemokines.
Article
Immunology
Matthew J. J. Butcher, Rama Krishna Gurram, Xiaoliang Zhu, Xi Chen, Gangqing Hu, Vanja Lazarevic, Keji Zhao, Jinfang Zhu
Summary: In this study, the researchers found that GATA3, a master transcription factor for Th2 cell differentiation, is also dynamically expressed in Th17 cells during their differentiation. Early deletion of Gata3 limited the pathogenicity of Th17 cells during EAE, while late deletion resulted in a failure to induce EAE symptoms. This highlights the critical role of GATA3 in promoting and maintaining the pathogenicity of T-bet-expressing Th17 cells in EAE.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Endocrinology & Metabolism
Di Wu, Zongxian Li, Yime Zhang, Yinlian Zhang, Guanqun Ren, Yanyu Zeng, Huiying Liu, Weiqiang Guan, Xingyu Zhao, Peng Li, Luni Hu, Zhiyuan Hou, Jingjing Gong, Jun Li, Wenfei Jin, Zeping Hu, Changtao Jiang, Houhua Li, Chao Zhong
Summary: This study reveals the importance of proline uptake in the activation of innate lymphoid cells and its contribution to gut homeostasis. Deficiency in proline uptake impairs lymphoid tissue inducer cell activation and worsens colitis. The study highlights the role of proline metabolism in specific subsets of lymphoid cells and its involvement in the regulation of reactive oxygen species and interleukin-22.
Article
Immunology
Zhishuo Wang, Chenghua Yan, Qizhen Du, Yuying Huang, Xuezhen Li, Dan Zeng, Ruizhi Mao, Rama Krishna Gurram, Shipeng Cheng, Wangpeng Gu, Lin Zhu, Weiguo Fan, Liyan Ma, Zhiyang Ling, Ju Qiu, Dangsheng Li, Enmei Liu, Yaguang Zhang, Yiru Fang, Jinfang Zhu, Bing Sun
Summary: This study found a negative correlation between the neurotransmitter serotonin and the cytokines IL-5 and IL-13 produced by ILC2s, which are related to depression. Serotonin can alleviate lung inflammation by suppressing ILC2 activation. The serotonin receptor HTR2A is highly expressed on ILC2s and can be targeted with an agonist called DOI to inhibit ILC2 activation and reduce type 2 immune response. Targeting HTR2A on ST2(+) ILC2s could be a potential treatment strategy for type 2 lung inflammation.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)