Review
Immunology
Yingyu Qin, Xueyang Bao, Mingzhu Zheng
Summary: CD8(+) T cells from the adaptive immune system and iNKT cells from the innate-like T lymphocytes both play important roles in defending against infections and cancers. CD8(+) T cell-based immunotherapy is a promising approach for the eradication of tumor cells, and iNKT cells contribute to CD8(+) T cell immunity through cross-priming and memory formation. This review also discusses recent advances in understanding the mechanisms of memory CD8(+) T cell differentiation and aging-induced impairment of T cell immunity.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Eric Y. Helm, Tomas Zelenka, Valeriu B. Cismasiu, Shamima Islam, Leonardo Silvane, Beatrice Zitti, Tim D. Holmes, Theodore T. Drashansky, Alexander J. Kwiatkowski, Christine Tao, Joseph Dean, Alyssa N. Obermayer, Xianghong Chen, Benjamin G. Keselowsky, Weizhou Zhang, Zhiguang Huo, Liang Zhou, Brian S. Sheridan, Jose R. Conejo-Garcia, Timothy I. Shaw, Yenan T. Bryceson, Dorina Avram
Summary: In this study, the role of the transcription factor Bcl11b in TRM cells was investigated during infection with Listeria monocytogenes. Conditional deletion of Bcl11b resulted in increased numbers of intestinal TRM cells, decreased splenic effector and circulating memory cells, and altered transcriptional programs in TRM cells with decreased expression of multipotent/multifunctional genes and upregulation of effector genes.
SCIENCE IMMUNOLOGY
(2023)
Article
Virology
Julia M. DeRogatis, Emily N. Neubert, Karla M. Viramontes, Monique L. Henriquez, Dequina A. Nicholas, Roberto Tinoco
Summary: CD38 expression regulates the survival and metabolism of CD8(+) T cells during acute and chronic viral infections. Higher CD38 levels are observed during chronic infection, leading to T cell exhaustion. CD38 has a dual cell-intrinsic function in limiting proliferation and function while promoting the survival of CD8(+) T cells.
JOURNAL OF VIROLOGY
(2023)
Article
Oncology
Shalu Sharma Kharkwal, Christopher T. Johndrow, Natacha Veerapen, Himanshu Kharkwal, Noemi A. Saavedra-Avila, Leandro J. Carreno, Samantha Rothberg, Jinghang Zhang, Scott J. Garforth, Peter J. Jervis, Lianjun Zhang, Alena Donda, Amareeta K. Besra, Liam R. Cox, Steven C. Almo, Alan Howell, Elizabeth E. Evans, Maurice Zauderer, Gurdyal S. Besra, Steven A. Porcelli
Summary: A novel bispecific T-cell engager (BiTE) was developed to activate iNKT cells for antitumor immunity, enhancing multiple effector functions and promoting tumor-specific CD8(+) cytolytic T-cell responses. Simultaneous checkpoint blockade with anti-CTLA-4 antibodies further enhanced the antitumor effects, providing a potential approach for combination immunotherapy. Multiple injections of covalently stabilized iNKT cell-specific BiTEs led to effective and nontoxic cancer immunotherapy regimens without inducing anergy or exhaustion in responding iNKT cells.
Article
Immunology
Lalit K. Beura, Milcah C. Scott, Mark J. Pierson, Vineet Joag, Sathi Wijeyesinghe, Matthew R. Semler, Clare F. Quarnstrom, Kathleen Busman-Sahay, Jacob D. Estes, Sara E. Hamilton, Vaiva Vezys, David H. O'Connor, David Masopust
Summary: Lymphocytic choriomeningitis virus (LCMV) is a natural mouse pathogen that can cause chronic infection. In this study, a new strain called LCMV-Minnesota (LCMV-MN) was isolated and characterized. Infection with LCMV-MN in laboratory mice resulted in viral persistence, with CD8(+) T cells showing characteristics of exhausted cells. This study provides insights into the immune response to chronic infections and the regulation of response to PD-1 blockade.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Weijia Zhao, Yujia Wang, Xinwei Zhang, Jie Hao, Kunshan Zhang, Xiaojun Huang, Yingjun Chang, Hounan Wu, Rong Jin, Qing Ge
Summary: The delayed recovery and reduced numbers of iNKT cells in transplantation conditions are linked to defective generation of thymic iNKT precursors and impaired differentiation of subpopulations under the influence of TCR and co-stimulatory signaling.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Margaret R. Dunne, Johannes Wagener, Juergen Loeffler, Derek G. Doherty, Thomas R. Rogers
Summary: This review examines evidence on the human immune response to invasive fungal diseases, with a focus on unconventional lymphocytes such as NK cells, gamma/delta T cells, MAIT cells, iNKT cells, and ILC. Recent discoveries about the roles of these novel lymphocyte groups in antifungal immunity are discussed, and the potential for improving antifungal treatment options through a better understanding of lymphocyte actions is explored.
CLINICAL IMMUNOLOGY
(2021)
Article
Oncology
Zhen Lu, Eun-Ah Bae, Ioannis I. Verginadis, Hongru Zhang, Christina Cho, Noreen McBrearty, Subin S. George, J. Alan Diehl, Constantinos Koumenis, Linda M. Bradley, Serge Y. Fuchs
Summary: The immune suppressive factors in the tumor microenvironment can weaken the viability and activities of CD8 + T cells, and activating transcription factor-4 (ATF4) plays an important role in maintaining the survival and activities of CD8 + T cells in the tumor microenvironment.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Cell Biology
Xiang Li, Chen Jin, Qi Chen, Xihua Zheng, Di Xie, Qielan Wu, Lu Wang, Shiyu Bai, Huimin Zhang, Li Bai
Summary: Invariant NK T (iNKT) cells are enriched in the liver, where a liver-specific CD24(+) iNKT subset with high proliferation and metabolism activity is found but lower granzyme B production. The liver microenvironment also influences the differentiation of conventional T cells, leading to the generation of CD24(+) T cells with different functional characteristics. These findings suggest that the liver microenvironment may induce the generation of a liver-specific iNKT subset that plays a crucial role in maintaining liver homeostasis.
JOURNAL OF LEUKOCYTE BIOLOGY
(2022)
Article
Rheumatology
Cristina M. Padilla, Eleanor Valenzi, Tracy Tabib, Banafsheh Nazari, John Sembrat, Mauricio Rojas, Patrizia Fuschiotti, Robert Lafyatis
Summary: This study analyzed lymphoid subpopulations in SSc-ILD lung tissue using single-cell RNA sequencing and found activated NK cells, CD8(+) tissue resident memory T cells, and Treg cells in SSc-ILD lungs. The transition of CD8(+) T cells to tissue resident memory phenotype was observed in SSc-ILD.
Article
Multidisciplinary Sciences
Daniel F. Zegarra-Ruiz, Dasom V. Kim, Kendra Norwood, Myunghoo Kim, Wan-Jung H. Wu, Fatima B. Saldana-Morales, Andrea A. Hill, Shubhabrata Majumdar, Stephanie Orozco, Rickesha Bell, June L. Round, Randy S. Longman, Takeshi Egawa, Matthew L. Bettini, Gretchen E. Diehl
Summary: Humans and their microbiota have a mutually beneficial relationship, where microbiota provides nutritional benefits and protection, and humans provide a hospitable environment. Maintaining this relationship requires immune balance to contain commensal microorganisms and limit inflammatory responses. Intestinal microorganisms can be recognized by T cells with antigen-specificity.
Article
Immunology
Ryan Zander, Moujtaba Y. Kasmani, Yao Chen, Paytsar Topchyan, Jian Shen, Shikan Zheng, Robert Burns, Jennifer Ingram, Can Cui, Nikhil Joshi, Joseph Craft, Allan Zajac, Weiguo Cui
Summary: This study found that CD4(+) T cells consist of three distinct subsets during chronic viral infection, and IL-21 derived from Tfh cells is critical for sustaining CD8(+) T cell responses and viral control.
Article
Oncology
Young Min Chung, Pragya P. Khan, Hong Wang, Wen-Bin Tsai, Yanli Qiao, Bo Yu, James W. Larrick, Mickey C-T Hu
Summary: The study explored the efficacy of low-dose antineoplastic agents SN-38 or metformin in sensitizing unresponsive tumors to respond to immune-checkpoint blockade therapy. Results showed these agents could suppress c-Myc and STAT3 through FOXO3 activation, thus boosting antitumor immunity by promoting NK and CD8+ T cell infiltration in the tumor microenvironment. These findings offer potential insights for improving patient responses to immunotherapy for tumors.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Allergy
Robert Ose, Benno Weigmann, Detlef Schuppan, Ari Waisman, Joachim Saloga, Iris Bellinghausen
Summary: CD56(+)CD3(+) iNKT cells promote allergen-specific gut and lung inflammation in PBMC-engrafted humanized mice, opening up new possibilities for therapeutic intervention in allergic diseases.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Anze Yu, Jinfei Fu, Zheng Yin, Hui Yan, Xiang Xiao, Dawei Zou, Xiaolong Zhang, Xiongbing Zu, Xian C. Li, Wenhao Chen
Summary: This study investigates the function of interferon regulatory factor 4 (IRF4) in antitumor CD8+ T cells and finds that sustained expression of IRF4 is crucial for maintaining CD8+ T cell immunity. These findings carry significant implications for the development of more potent immunotherapies for solid tumors.
Article
Multidisciplinary Sciences
Mingzhu Zheng, Kairui Mao, Difeng Fang, Dan Li, Jun Lyu, Dingkang Peng, Xi Chen, Nikki Cannon, Gangqing Hu, Jiajia Han, Keji Zhao, Wanjun Chen, Jinfang Zhu
Summary: IgA production in the gut relies on IgA-producing plasma cells derived from conventional B cells, with T cells and helper-like ILCs playing crucial roles in the formation of lymphoid structures in the gut. However, the functions of non-LTi helper-like ILCs in promoting IgA production are still not well understood.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
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
Rama K. Gurram, Danping Wei, Qiao Yu, Olena Kamenyeva, Hyunwoo Chung, Mingzhu Zheng, Matthew J. J. Butcher, Juraj Kabat, Chengyu Liu, Jaspal S. S. Khillan, Jinfang Zhu
Summary: In this study, novel GATA3 reporter mouse strains were used to investigate the expression and function of GATA3 in Th2 cells and ILC2 cells. The results revealed that GATA3 is dispensable for regulating its own expression in mature type 2 lymphocytes, and GATA3-deficient ILC2s might be more stable in vivo than in vitro.
FRONTIERS IN IMMUNOLOGY
(2022)
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
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
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)