Article
Immunology
Ester Leno-Duran, Sze-Ling Ng, Jack L. Strominger
Summary: The humanized double transgenic mice expressing both HLA-DR15 and TCR.Ob1A12 fail to quickly develop autoimmune encephalomyelitis, but the disease frequency increases significantly with age. The diseased mice show a decrease in IL-10-secreting regulatory T cells and have smaller spleens compared to non-diseased mice in the colony.
Article
Immunology
Hana Zdimerova, Anita Murer, Christine Engelmann, Ana Raykova, Yun Deng, Cornelia Gujer, Julia Ruhl, Donal McHugh, Nicole Caduff, Reza Naghavian, Gaetana Pezzino, Riccarda Capaul, Andrea Zbinden, Guido Ferlazzo, Jan D. Lunemann, Roland Martin, Bithi Chatterjee, Christian Munz
Summary: The immune responses to Epstein-Barr virus (EBV) infection along with the main genetic risk factor HLA-DR15 are shown to synergize in increasing the likelihood of developing multiple sclerosis (MS) sevenfold. The study observed elevated activation of both CD4(+) and CD8(+) T cells in HLA-DR15 donor-reconstituted humanized mice, even when compared to those carrying HLA-DR4 which is associated with other autoimmune diseases. Despite the higher immune activation, EBV viral loads were less well controlled in the context of HLA-DR15, and CD4(+) T cell clones demonstrated cross-reactivity towards allogeneic target cells and an MS autoantigen.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Immunology
Xiaoran Ma, Shuang Wang, Chenglin Li, Xihui Jia, Tiantian Wang, Zhe Leng, Ran Lu, Xiaowen Kong, Jinyu Zhang, Ling Li
Summary: Baicalein (BAI), a natural flavonoid, has been found to alleviate clinical symptoms, demyelination, and inflammatory response in EAE mice. It inhibits M1 microglia/macrophage activation, decreases the expression of proinflammatory cytokines, and targets STAT1 to inhibit polarization. These findings suggest the potential use of BAI in the treatment of MS.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Oncology
Noriaki Tsuji, Kohei Hosokawa, Ryota Urushihara, Mikoto Tanabe, Takamasa Katagiri, Tatsuhiko Ozawa, Hiroyuki Takamatsu, Ken Ishiyama, Hirohito Yamazaki, Hiroyuki Kishi, Seishi Ogawa, Shinji Nakao
Summary: This study demonstrates that antigens presented by HSPCs on HLA-DR15 may lead to abnormal activation of CD4(+) T cells and immune escape in the development of AA. Immune response-related gene expression is downregulated in DR(-) cells compared to HLA-I(-) HSPCs.
Article
Neurosciences
Carolina Melero-Jerez, Beatriz Fernandez-Gomez, Rafael Lebron-Galan, Maria Cristina Ortega, Irene Sanchez-de Lara, Ana Cristina Ojalvo, Diego Clemente, Fernando de Castro
Summary: The relapsing-remitting form of multiple sclerosis (MS) is characterized by symptomatic phases followed by periods of partial or total recovery, and patients with MS may benefit from endogenous agents controlling the inflammatory process and promoting remyelination. Myeloid-derived suppressor cells (MDSCs) show potential anti-inflammatory effects and influence oligodendrocyte precursor cells (OPCs) in MS animal models, offering insight into developing therapies for effective myelin preservation and repair in MS patients.
Review
Immunology
Jang Hyun Park, In Kang, Heung Kyu Lee
Summary: gamma delta T cells, expressing gamma delta T cell receptor instead of alpha beta T cell receptor, play critical roles in multiple physiological systems and diseases. They are preferentially located at mucosal surfaces, such as the gut, and can also be found in the meninges in the central nervous system. Recent findings suggest their importance in brain function, homeostasis, and regulating inflammatory responses, particularly in neurodegenerative diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Mahdia Benkhoucha, Ngoc Lan Tran, Gautier Breville, Isis Senoner, Paul F. Bradfield, Thalia Papayannopoulou, Doron Merkler, Thomas Korn, Patrice H. Lalive
Summary: CD4(+)c-Met(+) T cells are increased in multiple sclerosis models and exhibit a pro-inflammatory phenotype with enhanced adhesion and migration.
JOURNAL OF NEUROINFLAMMATION
(2022)
Review
Clinical Neurology
Daniel B. Rubin, Henrikas Vaitkevicius
Summary: CAR T cell therapy is crucial in treating advanced malignancies, but is linked to significant neurologic toxicity. Despite increasing clinical experience, the unpredictability of neurologic symptoms remains a major source of anxiety for both patients and practitioners, presenting a barrier to broader adoption of this treatment modality.
JOURNAL OF THE NEUROLOGICAL SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Michal K. Zarobkiewicz, Izabela Morawska, Adam Michalski, Jacek Rolinski, Agnieszka Bojarska-Junak
Summary: NKT cells, especially iNKT cells, may play a key role in autoimmune diseases. Researchers summarized the results of NKT-oriented studies in major neurological autoimmune diseases such as multiple sclerosis, myasthenia gravis, and Guillain-Barre syndrome.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Immunology
Jaydeep Bhat, Katarzyna Placek, Simon Faissner
Summary: Gamma delta T cells are unconventional T cells that play pleiotropic roles in diseases, producing various cytokines and engaging different immune response mechanisms based on environmental cues. Their dichotomous nature contributes to beneficial or detrimental responses in cancer, neuroimmunology, and infectious diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Xiaoxiao Jin, Xiaotao Liu, Zining Zhou, Yan Ding, Yandan Wu, Jie Qiu, Chuanlai Shen
Summary: In this study, 25 HLA-A0201 restricted GPC3 epitopes were predicted and 5 were identified as real-world epitopes for specific CD8(+) T cell activation. These epitopes were further confirmed to induce robust CD8(+) T cell responses and cytotoxicity targeting HepG2 cells, providing potential for the development of T cell epitope vaccines and evaluation of GPC3 specific T cell responses.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Immunology
Jasmina Bier, Sebastian M. Steiger, Holger M. Reichardt, Fred Luehder
Summary: The study investigated the impact of antigen priming on the sensitivity of T cells to glucocorticoid-induced apoptosis, revealing the different responses of antigen-primed effector T cells compared to naïve T cells to synthetic GCs in vitro and in vivo. The findings suggest that antigen priming influences the sensitivity of T cells to therapeutic GCs in the context of inflammatory diseases.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Agricultural Engineering
B. Babinszki, Z. Sebestyen, E. Jakab, L. Kohalmi, J. Bozi, G. Varhegyi, L. Wang, O. Skreiberg, Zs Czegeny
Summary: Slow pyrolysis of spruce and birch was conducted under different heating programs and conditions in a quartz tube reactor heated by an electric furnace. The study found that spruce produced more char yield than birch, and the main gaseous products showed similar evolution profiles. The relative amount of aromatic and polyaromatic compounds in volatile matter decreased significantly with increasing carbonization temperature.
BIORESOURCE TECHNOLOGY
(2021)
Article
Behavioral Sciences
Guilherme Bauer-Negrini, Iohanna Deckmann, Gustavo Brum Schwingel, Mauro Mozael Hirsch, Mellanie Fontes-Dutra, Giovanna Carello-Collar, Diane E. Halliwell, Maria Paraskevaidi, Camilo L. M. Morais, Francis L. Martin, Rudimar Riesgo, Carmem Gottfried, Victorio Bambini-Junior
Summary: This study investigated the impact of T-cell immunodeficiency on behaviors relevant to neurodevelopmental and neuropsychiatric disorders and characterized related alterations through multidisciplinary approaches. Results showed that BALB/c nude mice displayed impaired sociability, a complex pattern of repetitive behaviors, and increased sensitivity to thermal nociception, along with a different CNS spectrochemical signature compared to their heterozygous littermates. These findings highlight potential neuroimmunological influences involved with the observed alterations.
BEHAVIOURAL BRAIN RESEARCH
(2022)
Review
Immunology
Martin Diebold, Luca Fehrenbacher, Maximilian Frosch, Marco Prinz
Summary: Experimental autoimmune encephalomyelitis (EAE) is an animal model used to mimic multiple sclerosis (MS), with the innate immune response playing a key role in both acute and chronic stages of MS. The composition and roles of microglia, CNS resident myeloid units, and infiltrating myeloid cells differ during EAE, with specific myeloid cell types and states being responsible for antigen presentation and disease propagation. Single-cell techniques offer insight into proinflammatory and beneficial cell states, as well as identification of potential treatment targets for EAE.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Rebekah A. Warwick, Nathali Kaushansky, Nimrod Sarid, Amir Golan, Michal Rivlin-Etzion
Article
Biochemistry & Molecular Biology
Waleed Minzel, Avanthika Venkatachalam, Avner Fink, Eric Hung, Guy Brachya, Ido Burstain, Maya Shaham, Amitai Rivlin, Itay Omer, Adar Zinger, Shlomo Elias, Eitan Winter, Paul E. Erdman, Robert W. Sullivan, Leah Fung, Frank Mercurio, Dansu Li, Joseph Vacca, Nathali Kaushansky, Liran Shlush, Moshe Oren, Ross Levine, Eli Pikarsky, Irit Snir-Alkalay, Yinon Ben-Neriah
Article
Immunology
Nathali Kaushansky, Eszter Bakos, Shirty Becker-Herman, Idit Shachar, Avraham Ben-Nun
JOURNAL OF IMMUNOLOGY
(2019)
Article
Immunology
N. Kaushansky, A. Kaminitz, H. Allouche-Arnon, A. Ben-Nun
JOURNAL OF NEUROIMMUNOLOGY
(2019)
Letter
Hematology
Tal Shahar Gabay, Non Chapal-Ilani, Yoni Moskovitz, Tamir Biezuner, Barak Orott, Yardena Brilon, Anna Fridman-Dror, Rawan Sabah, Ran Balicer, Amos Tanay, Netta Mendelson-Cohen, Eldad J. Dann, Riva Fineman, Nathali Kaushansky, Shlomit Yehudai-Reshef, Tsila Zuckerman, Liran I. Shlush
Article
Hematology
Sigal Tavor, Tali Shalit, Noa Chapal Ilani, Yoni Moskovtiz, Nir Livnat, Yoram Groner, Haim Barr, Mark D. Minden, Alexander Plotnikov, Michael W. Deininger, Nathali Kaushansky, Liran I. Shlush
Article
Cell Biology
Lea Ankri, Elishai Ezra-Tsur, Shir R. Maimon, Nathali Kaushansky, Michal Rivlin-Etzion
Article
Cell & Tissue Engineering
Rina Zilkha-Falb, Nathali Kaushansky, Avraham Ben-Nun
Article
Multidisciplinary Sciences
Tzah Feldman, Akhiad Bercovich, Yoni Moskovitz, Noa Chapal-Ilani, Amanda Mitchell, Jessie J. F. Medeiros, Tamir Biezuner, Nathali Kaushansky, Mark D. Minden, Vikas Gupta, Michael Milyavsky, Zvi Livneh, Amos Tanay, Liran I. Shlush
Summary: Recurrent deletions in myeloid malignancies are found to be generated by PARP1-dependent microhomology-mediated end joining, originating in pre-leukemic stem cells. The association between POLQ-independent MMEJ and clonal hematopoiesis is demonstrated, shedding light on mutational mechanisms in the early stages of leukemia evolution.
NATURE COMMUNICATIONS
(2021)
Editorial Material
Biochemistry & Molecular Biology
Nili Furer, Nathali Kaushansky, Liran I. Shlush
Article
Hematology
Amos Tuval, Yardena Brilon, Hadas Azogy, Yoni Moskovitz, Dena Leshkowitz, Tomer M. Salame, Mark D. Minden, Perry Tal, Varda Rotter, Moshe Oren, Nathali Kaushansky, Liran Shlush
Summary: Pre-leukemic clones carrying DNMT3A mutations have inherent chemoresistance and selective advantage. They also have a dominant pseudo-mutant P53 conformation. Shifting the dynamic equilibrium in favor of the wild-type P53 conformation can eliminate dysfunctional cells.
Article
Hematology
Kyoung Ha Kim, TaeHyung Kim, Igor Novitzky-Basso, Hyewon Lee, Youngseok Yoo, Jae-Sook Ahn, Ivan Pasic, Arjun Law, Wilson Lam, Fotios Michelis, Armin Gerbitz, Auro Viswabandya, Jeffrey Lipton, Rajat Kumar, Jonas Mattsson, Zhaolei Zhang, Nathali Kaushansky, Yardena Brilon, Noa Chapal-Ilani, Tamir Biezuner, Liran I. Shlush, Dennis Dong Hwan Kim
Summary: It is unknown whether donor clonal hematopoiesis affects transplant outcomes after allogeneic hematopoietic stem cell transplantation (HSCT). In this study, 744 samples from HSCT recipients and corresponding donors were analyzed, and the presence of clonal hematopoiesis with indeterminate potential (CHIP) mutations in donors did not impact overall survival, relapse incidence, non-relapse mortality, graft-versus-host disease rates, or secondary malignancy occurrence following HSCT. These findings suggest that molecular profiling for CHIP mutations may not be necessary for pretransplant evaluation of stem cell donors.
Article
Multidisciplinary Sciences
N. Zioni, A. Akhiad Bercovich, N. Chapal-Ilani, Tal Bacharach, N. Rappoport, A. Solomon, R. Avraham, E. Kopitman, Z. Porat, M. Sacma, G. Hartmut, M. Scheller, C. Muller-Tidow, D. Lipka, E. Shlush, M. Minden, N. Kaushansky, Liran Shlush
Summary: The accumulation of fatty bone marrow and somatic mutations in hematopoietic stem cells (HSCs) increases with aging. In preclinical mouse models, it is found that fatty bone marrow can enhance the self-renewal of HSCs and activate inflammatory signaling. The inflammatory cytokines, such as IL-6, in fatty bone marrow promote DNMT3a-driven clonal hematopoiesis, which can be inhibited by blocking the IL-6 pathway.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Aster Legesse, Nathali Kaushansky, Ilana Braunstein, Haddas Saad, Gerardo Lederkremer, Ami Navon, Ariel Stanhill
Summary: Protein quality control is a crucial process to monitor the folding status of proteins. RNF149, a membrane bound E3 ligase, plays a significant role in maintaining cellular functionality by ubiquitinating non-translocated proteins. Dysfunction of RNF149 leads to disruption of cellular quality control and is associated with pathological conditions related to impaired quality control.
COMMUNICATIONS BIOLOGY
(2023)
Article
Genetics & Heredity
Tamir Biezuner, Yardena Brilon, Asaf Ben Arye, Barak Oron, Aditee Kadam, Adi Danin, Nili Furer, Mark D. Minden, Dennis Dong Hwan Kim, Shiran Shapira, Nadir Arber, John Dick, Paaladinesh Thavendiranathan, Yoni Moskovitz, Nathali Kaushansky, Noa Chapal-Ilani, Liran Shlush
Summary: Deep targeted sequencing technologies are not widely used in clinical practice due to complexity and cost. In this study, we sequenced a large cohort using Molecular Inversion Probes (MIP) technology and improved its performance in detecting low frequency variants and GC rich regions through statistical model enhancements and biochemical modifications.
NAR GENOMICS AND BIOINFORMATICS
(2022)