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
Biochemistry & Molecular Biology
Michio Shimamura, Shin-ichi Kamijo, Petr Illarionov
Summary: Helicobacter pylori extracts cholesterol from the host and converts it to its glycosides. It has been found that iNKT cells can recognize the cholesteryl glycosides produced by H. pylori and activate immune responses through a Mincle-dependent pathway. These findings provide insights into the immune mechanisms against H. pylori infection.
Article
Cell Biology
Theresa E. Pankhurst, Kaitlin H. Buick, Joshua L. Lange, Andrew J. Marshall, Kaileen R. Button, Olga R. Palmer, Kathryn J. Farrand, Isabelle Montgomerie, Thomas W. Bird, Ngarangi C. Mason, Joanna Kuang, Benjamin J. Compton, Davide Comoletti, Mariolina Salio, Vincenzo Cerundolo, Miguel E. Quinones-Mateu, Gavin F. Painter, Ian F. Hermans, Lisa M. Connor
Summary: Protective immune responses against respiratory pathogens largely depend on mucosal immunity, but most licensed vaccines fail to induce sufficient mucosal immunity. A suitable mucosal adjuvant has been lacking for the development of safe and effective mucosal vaccines. This study explores the use of mucosal-associated invariant T (MAIT) cells as adjuvants, showing that intranasal immunization with MAIT cell agonists and viral proteins can induce protective humoral immunity and IgA production.
Article
Immunology
Travis Shute, Eyal Amiel, Noran Alam, Jennifer L. Yates, Katya Mohrs, Elizabeth Dudley, Briana Salas, Chloe Mesa, Adriana Serrata, Daniel Angel, Brandy K. Vincent, Amanda Weyers, Paula A. Lanthier, Emilie Vomhof-Dekrey, Rachel Fromme, Mitchell Laughlin, Olivia Durham, Jianjun Miao, Devon Shipp, Robert J. Linhardt, Kelly Nash, Elizabeth A. Leadbetter
Summary: CD4(+) T cells play a crucial role in facilitating B cell immune protection provided by vaccines, while iNKT cells have been identified as an alternative source of help for B cells in mice. Nanoparticles containing alpha GC and S. pneumoniae polysaccharides activate murine iNKT cells and B cells, inducing robust immune responses and protection against deadly pathogens. However, the potential of these nanoparticles to eliminate B cells under certain conditions suggests the need for further clarification on iNKT cell interactions with B cells.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Cell Biology
Hongyu Jia, Jianing Chen, Xujun Zhang, Kefan Bi, Hetong Zhou, Tianxing Liu, Jia Xu, Hongyan Diao
Summary: This study investigated the role of T cell subsets in primary biliary cholangitis (PBC) patients and found that these patients had higher levels of invariant natural killer T (iNKT) cells and CD3(+)CD56(+) alpha Galcer-CD1d tetramer(-) T cells compared to healthy controls. These T cell subsets also produced significantly higher levels of Interleukin-17A (IL-17A) in PBC patients and the levels were positively correlated with disease severity. The study also revealed that stimulation of autoantibodies in PBC patients increased the production of IL-17A by these T cell subsets, which promoted PBC-related fibrosis. These findings provide evidence-based diagnostic and therapeutic strategies for PBC patients.
JOURNAL OF LEUKOCYTE BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Wafaa S. Khalaf, Mohammad R. A. Mahmoud, Walid F. Elkhatib, Hany R. Hashem, Wafaa E. Soliman
Summary: The study found that DPNKT-like cell subset, IL-2, and IFN-gamma levels are significantly elevated in URM patients, and these parameters are also increased after pregnancy, serving as markers to predict the risk of miscarriage.
Article
Immunology
Gloria Delfanti, Filippo Cortesi, Alessandra Perini, Gaia Antonini, Laura Azzimonti, Claudia de Lalla, Claudio Garavaglia, Mario L. Squadrito, Maya Fedeli, Michela Consonni, Silvia Sesana, Francesca Re, Haifa Shen, Paolo Dellabona, Giulia Casorati
Summary: Adoptive immunotherapy using T cells engineered with tumor-specific TCRs holds promise for cancer treatment. In this study, researchers harnessed iNKT cells with a second TCR specific for a tumor-associated peptide to generate bispecific effectors for CD1d- and MHC-restricted antigens. The TCR-engineered iNKT cells demonstrated high efficacy in restraining tumor progression and achieved robust cancer control by simultaneously modulating intratumoral suppressive myeloid populations and killing malignant cells. These findings support the potential use of tumor-redirected TCR-iNKT cells and local alpha-GalCer boosting as a therapy for cancer patients.
SCIENCE IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Niloofar Amirian, Reza Ranjbaran, Negin Shokrgozar, Saeed Ataei, Asghar Bazrafshan, Sedigheh Sharifzadeh
Summary: The study demonstrated a significant imbalance in the ratio of iNKT cell subsets in favor of IL-4 producing cells in alloimmunized thalassemia patients, potentially serving as a mechanism for antibody responses.
Article
Immunology
Guangwei Cui, Akihiro Shimba, Jianshi Jin, Taisaku Ogawa, Yukiko Muramoto, Hitoshi Miyachi, Shinya Abe, Takuma Asahi, Shizue Tani-Ichi, Johannes M. Dijkstra, Yayoi Iwamoto, Kirill Kryukov, Yuanbo Zhu, Daichi Takami, Takahiro Hara, Satsuki Kitano, Yan Xu, Hajime Morita, Moyu Zhang, Lynn Zreka, Keishi Miyata, Takashi Kanaya, Shinya Okumura, Takashi Ito, Etsuro Hatano, Yoshimasa Takahashi, Hiroshi Watarai, Yuichi Oike, Tadashi Imanishi, Hiroshi Ohno, Toshiaki Ohteki, Nagahiro Minato, Masato Kubo, Georg A. Hollander, Hideki Ueno, Takeshi Noda, Katsuyuki Shiroguchi, Koichi Ikuta
Summary: This study reveals a circulating subset of iNKT cells, C2 iNKT cells, with NK cell-like properties distinct from conventional tissue-resident iNKT cells. C2 iNKT cells protect against tumor metastasis and promote antiviral immune responses.
SCIENCE IMMUNOLOGY
(2022)
Article
Immunology
Georgina V. Hopkins, Stella Cochrane, David Onion, Lucy C. Fairclough
Summary: This study reveals that iNKT cells are more abundant in peanut-allergic adults compared to non-allergic adults, and peanut lipid-exposed iNKT cells resulted in the identification of a subset of CD8(+) iNKT cells significantly lower in peanut-allergic adults.
FRONTIERS IN IMMUNOLOGY
(2023)
Editorial Material
Oncology
Luc Van Kaer
Summary: A study shows that the transcription factor LEF1 can optimize the functional properties of iNKT cells and enhance their antitumor immunity, suggesting the potential of developing robust cancer immunotherapies based on CAR-modified iNKT cells.
CANCER IMMUNOLOGY RESEARCH
(2023)
Article
Cell Biology
Mallory Paynich Murray, Catherine M. Crosby, Paola Marcovecchio, Nadine Hartmann, Shilpi Chandra, Meng Zhao, Archana Khurana, Sonja P. Zahner, Bjorn E. Clausen, Fadie T. Coleman, Joseph P. Mizgerd, Zbigniew Mikulski, Mitchell Kronenberg
Summary: This study investigates the roles of innate-like T cells during pulmonary pneumococcal infection. The researchers found that these T cells rapidly increase in the lung tissue following infection and participate in the immune response. Specifically, interleukin-17-producing NKT17 and gamma delta T cells play a major role in the infection, with NKT17 cells being preferentially located in lung tissue prior to infection and interacting with CD103(+) dendritic cells. These studies demonstrate the importance of specific cellular interactions and functional subsets of innate-like T cells in protecting against lung infection.
Article
Pharmacology & Pharmacy
Hongbo Zhang, Yuzhen Zhuo, Dihua Li, Lanqiu Zhang, Qiaoying Gao, Lei Yang, Xiangfei Yuan
Summary: This study aimed to investigate the effect of Dihydroartemisinin (DHA) on inducing ferroptosis and activating anti-tumor immunity and the underlying molecular mechanism. The results showed that DHA inhibited pancreatic cancer cell proliferation and induced cell ferroptosis by up-regulating the expression of P53 and ALOX12, while also up-regulating the expression of GPX4 and SLC7A11. Furthermore, DHA reduced the suppressive expansion of M2 and MDSCs, and increased the population of CD8(+)T cells, NK cells and NKT cells in tumor tissues.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Jian Wang, Yu Wen, Shi-Hao Zhou, Hai-Wei Zhang, Xiao-Qian Peng, Ru-Yan Zhang, Xu-Guang Yin, Hong Qiu, Rui Gong, Guang-Fu Yang, Jun Guo
Summary: Conjugating the potent invariant natural killer T cell (iNKT) agonist alpha-Galactosylceramide (alpha GalCer) to the receptor-binding domain (RBD) of the viral spike protein resulted in a conjugate vaccine that induced stronger immune responses and cross-neutralization against various variants.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Immunology
Owen Jensen, Shubhanshi Trivedi, Jeremy D. Meier, Keke C. Fairfax, J. Scott Hale, Daniel T. Leung
Summary: Mucosal-associated invariant T (MAIT) cells are innate-like T lymphocytes that protect mucosal surfaces against bacterial pathogens. They not only release inflammatory cytokines and cytotoxic molecules but also provide B cell help. This study identifies a population of CXCR5(+) T follicular helper-like MAIT cells (MAITfh) that can provide B cell help within mucosal lymphoid organs.
SCIENCE IMMUNOLOGY
(2022)
Review
Immunology
Fatma Zehra Hapil, Gerhard Wingender
Letter
Immunology
Shilpi Chandra, Gerhard Wingender, Jason A. Greenbaum, Mitchell Kronenberg
JOURNAL OF IMMUNOLOGY
(2018)
Article
Immunology
Shilpi Chandra, Gerhard Wingender, Jason A. Greenbaum, Archana Khurana, Amin M. Gholami, Anusha-Preethi Ganesan, Michael Rosenbach, Katy Jaffee, James E. Gern, Robert Wood, George O'Connor, Megan Sandel, Meyer Kattan, Leonard Bacharier, Alkis Togias, Anthony A. Horner, Mitchell Kronenberg
JOURNAL OF IMMUNOLOGY
(2018)
Review
Oncology
Duygu Sag, Zeynep Ozge Ayyildiz, Sinem Gunalp, Gerhard Wingender
Article
Genetics & Heredity
Vivek Chandra, Sourya Bhattacharyya, Benjamin J. Schmiedel, Ariel Madrigal, Cristian Gonzalez-Colin, Stephanie Fotsing, Austin Crinklaw, Gregory Seumois, Pejman Mohammadi, Mitchell Kronenberg, Bjoern Peters, Ferhat Ay, Pandurangan Vijayanand
Summary: This study utilized H3K27ac HiChIP analysis to identify promoter-interacting expression quantitative trait loci (pieQTLs) in five common immune cell types, showing the importance of these variants in gene regulation. Additionally, the study presents a method for functional eQTL discovery and provides insights into the relevance of noncoding variants for cell-specific gene regulation and disease association.
Article
Multidisciplinary Sciences
Muge Ozkan, Yusuf Cem Eskiocak, Gerhard Wingender
Summary: The identification of immune effector functions, particularly those involving IL-10 production, is crucial for understanding immune responses. While IL-10(GFP) reporter lines can accurately report on IL-10 production by lymphoid cells, they may not be suitable for analyzing myeloid cell IL-10 production, as autofluorescence can interfere with GFP signals. This highlights a potential technical limitation when using GFP-reporter lines for studying myeloid cells in inflammation.
Article
Biochemistry & Molecular Biology
Meng Zhao, Ariel Quintana, Chen Zhang, Alexander Y. Andreyev, William Kiosses, Tomomi Kuwana, Anne Murphy, Patrick G. Hogan, Mitchell Kronenberg
Summary: The differentiation of NKT2 cells requires higher and sustained calcium signals compared to their NKT1 counterparts, which is connected with mitochondria and cellular metabolism.
Article
Multidisciplinary Sciences
Muge Ozkan, Yusuf Cem Eskiocak, Gerhard Wingender
Summary: Asthma is a heterogeneous disease that can be classified into eosinophilic asthma and neutrophilic asthma. Eosinophilic asthma is treatment-responsive and associated with allergic asthma, while neutrophilic asthma is treatment-resistant. Understanding the differences between these endotypes is crucial for developing effective diagnosis and treatment strategies.
Article
Immunology
Jihye Han, Qingqing Wan, Goo-Young Seo, Kenneth Kim, Sarah El Baghdady, Jee H. Lee, Mitchell Kronenberg, Yun-Cai Liu
Summary: Hypoxia plays an important role in airway inflammation and remodeling in lung diseases. This study focuses on understanding how hypoxic pulmonary epithelium regulates allergic inflammation. The researchers found that the VHL-HIF2 alpha axis mediates the hypoxic response, controlling pulmonary type 2 responses through increasing ADM expression and causing ILC2 activation.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Yusuf Cem Eskiocak, Zeynep Ozge Ayyildiz, Sinem Gunalp, Asli Korkmaz, Derya Goksu Helvaci, Yavuz Dogan, Duygu Sag, Gerhard Wingender
Summary: Various aspects of in vitro culture conditions, including elevated Ca2+ concentrations, can impact the functional response of immune cells. The presence of elevated Ca2+ concentrations during in vitro stimulation can increase cytokine production in both conventional and unconventional T cells, as well as B cells. However, primary human monocyte-derived macrophages showed increased cell death in the presence of elevated Ca2+ concentrations. Furthermore, elevated Ca2+ levels promoted M1 differentiation in macrophages. This study highlights the importance of considering the Ca2+ concentration in in vitro cultures for functional experiments and the potential of elevated Ca2+ levels to boost cytokine production in lymphoid cells.
Article
Multidisciplinary Sciences
Sibel Kalyoncu, Semiramis Yilmaz, Ayca Zeybek Kuyucu, Dogu Sayili, Olcay Mert, Hakan Soyturk, Seyda Gullu, Huseyin Akinturk, Erhan Citak, Merve Arslan, Melda Guray Taskinarda, Ibrahim Oguzhan Tarman, Gizem Yilmazer Altun, Ceren Ozer, Ridvan Orkut, Aysegul Demirtas, Idil Tilmensagir, Umur Keles, Ceren Ulker, Gizem Aralan, Yavuz Mercan, Muge Ozkan, Hasan Onur Caglar, Gizem Arik, Mehmet Can Ucar, Muzaffer Yildirim, Tugce Canavar Yildirim, Dilara Karadag, Erhan Bal, Aybike Erdogan, Serif Senturk, Serdar Uzar, Hakan Enul, Cumhur Adiay, Fahriye Sarac, Arzu Tas Ekiz, Irem Abaci, Ozge Aksoy, Hivda Ulbegi Polat, Saban Tekin, Stefan Dimitrov, Aykut Ozkul, Gerhard Wingender, Ihsan Gursel, Mehmet Ozturk, Mehmet Inan
Summary: Recombinant protein-based SARS-CoV-2 vaccines are developed to address the vaccine equity gap, especially for low-/middle-income countries. The vaccine utilizes the receptor binding domain of the SARS-CoV-2 Delta Plus strain (RBD-DP) and has shown high immunogenicity with both antibody and T-cell responses. It also demonstrates strong neutralizing activity against different strains of the virus and provides effective protection in mouse models.
SCIENTIFIC REPORTS
(2023)
Editorial Material
Rheumatology
Meng Zhao, Mitchell Kronenberg
ARTHRITIS & RHEUMATOLOGY
(2023)
Review
Immunology
Catherine M. Crosby, Mitchell Kronenberg
NATURE REVIEWS IMMUNOLOGY
(2018)
