Article
Chemistry, Medicinal
Horst Prescher, Astrid Schweizer, Martin Frank, Elena Kuhfeldt, Julia Ring, Lars Nitschke
Summary: The development of high affinity ligands for Siglecs is of significant interest due to their therapeutically relevant functions. This study introduces a new strategy for developing and designing Siglec ligands, using Siglec-2 (CD22) as an example, as disialyl-oligosaccharide mimetics. The study provides insights into the development and design of dimeric ligands with high affinity and avidity to cell surface-expressed CD22, as well as assay development, structure activity relationships, and biological data on calcium flux regulation in B-cells. State-of-the-art molecular dynamics simulations are used to model the binding modes of selected ligands, opening new perspectives for drug design efforts targeting Siglecs.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Immunology
Christopher M. Skopnik, Khlowd Al-Qaisi, Rosaleen A. Calvert, Philipp Enghard, Andreas Radbruch, Brian J. Sutton, Hiromi Kubagawa
Summary: This study identified critical amino acid residues of human Fc mu R for binding to IgM Fc, as well as the effects of certain residues on receptor expression and IgM binding. Results suggest specific sites and stretches within the Fc mu R structure that are essential for its proper function and interaction with IgM.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Xin Yang, Qiuxia Yu, Hao Xu, Jianfeng Zhou
Summary: Treatment failure or relapse in CART therapy due to reduction in target antigen expression is a challenge. Epigenetic drug Chidamide can enhance CD22 expression on B-cell tumor cells, improving the efficacy of CD22 CART therapy by affecting protein distribution.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Nicolas Rochereau, Eva Michaud, Louis Waeckel, Martin Killian, Remi Gayet, Roman Goguyer-Deschaumes, Xavier Roblin, Gilles Biolley, Blaise Corthesy, Stephane Paul
Summary: Recent studies have shown that SIgM can also undergo retrotranscytosis through M cells, indicating a potential role in regulating mucosal immunity.
Review
Immunology
William Royster, Ping Wang, Monowar Aziz
Summary: Siglec-G plays an important immunoregulatory role in B-1a cells and myeloid cells, contributing to the potential therapeutic approach in treating sepsis. A clear understanding of Siglec-G is crucial in developing novel therapeutics for sepsis.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Piper A. Robida, Clayton H. Rische, Netali Ben-Baruch Morgenstern, Rethavathi Janarthanam, Yun Cao, Rebecca A. Krier-Burris, Wouter Korver, Alan Xu, Thuy Luu, Julia Schanin, John Leung, Marc E. Rothenberg, Joshua B. Wechsler, Bradford A. Youngblood, Bruce S. Bochner, Jeremy A. O'Sullivan
Summary: Mast cells are tissue-resident cells that contribute to allergic diseases through excessive or inappropriate cellular activation and degranulation. Siglec-6, a receptor selectively expressed by mast cells, could be a promising target for therapeutic intervention. This study found that Siglec-6 is highly expressed by human mast cells and has a potent inhibitory effect on mast cell activation, making it a potential therapeutic target for mast cell-driven diseases.
Article
Allergy
Irina Miralda, Nyssa B. Samanas, Albert J. Seo, Jake S. Foronda, Josie Sachen, Yvonne Hui, Shane D. Morrison, Carole A. Oskeritzian, Adrian M. Piliponsky
Summary: This study demonstrates that Siglec-9 and its ligands play an important role in limiting human mast cell activation in vitro, reducing degranulation, arachidonic acid production, and chemokine release.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
James Brett Case, Samantha Mackin, John M. Errico, Zhenlu Chong, Emily A. Madden, Bradley Whitener, Barbara Guarino, Michael A. Schmid, Kim Rosenthal, Kuishu Ren, Ha Dang, Gyorgy Snell, Ana Jung, Lindsay Droit, Scott A. Handley, Peter J. Halfmann, Yoshihiro Kawaoka, James E. Crowe, Daved H. Fremont, Herbert W. Virgin, Yueh-Ming Loo, Mark T. Esser, Lisa A. Purcell, Davide Corti, Michael S. Diamond
Summary: SARS-CoV-2 Omicron variant strains are less susceptible to therapeutic neutralizing antibodies. However, therapeutic antibodies S309 and AZD7442 can still reduce lung infection in a mouse model. Different antibodies have different mechanisms of protection against Omicron variants.
NATURE COMMUNICATIONS
(2022)
Article
Immunology
Liting Wu, Yanjian Yang, Along Gao, Jun Li, Jianmin Ye
Summary: The study found that tilapia anterior kidney (AK) leukocytes can be divided into two subsets of IgM(+) B cells: lymphoid (L) gate and granulocyte-monocyte/macrophage (G-M) subsets. The G-M gate IgM(+) cells resemble plasma-like cells, with high antibody-secreting, phagocytic, and antigen-presenting capacities.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Zhenghao Wu, Junjie Zhou, Yunxiao Xiao, Jie Ming, Jing Zhou, Fang Dong, Xiaoqi Zhou, Zhuoshuo Xu, Xiangwang Zhao, Ping Lei, Tao Huang
Summary: In this study, the authors identified a subset of B cells called B-IR cells that have a memory phenotype and promote the response to immune checkpoint inhibitor (ICI) therapy. These cells were present in cancer-associated tertiary lymphoid structures and their gene signatures correlated with positive outcomes in patients treated with ICI therapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Yao Sun, Yongfeng Su, Yizhi Wang, Na Liu, Yuhang Li, Jianlin Chen, Zhuoqing Qiao, Jingwen Niu, Jiangwei Hu, Bin Zhang, Hongmei Ning, Liangding Hu
Summary: The study presented a case of a patient with B-ALL who experienced extramedullary relapse after allogeneic stem cell transplantation and underwent multiple CAR-T cell therapies, including different variants of CD19 CAR-T cells. The patient achieved therapeutic responses after some of the treatments, demonstrating the potential efficacy of CAR-T cell therapy in relapsed B-ALL patients.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Eris Bame, Hao Tang, Jeremy C. Burns, Million Arefayene, Klaus Michelsen, Bin Ma, Isaac Marx, Robin Prince, Allie M. Roach, Urjana Poreci, Douglas Donaldson, Patrick Cullen, Fergal Casey, Jing Zhu, Thomas M. Carlile, Dipen Sangurdekar, Baohong Zhang, Patrick Trapa, Joseph Santoro, Param Muragan, Alex Pellerin, Stephen Rubino, Davide Gianni, Bekim Bajrami, Xiaomei Peng, Alex Coppell, Katherine Riester, Shibeshih Belachew, Devangi Mehta, Mike Palte, Brian T. Hopkins, Matthew Scaramozza, Nathalie Franchimont, Michael Mingueneau
Summary: BIIB091 is a potent and selective small-molecule inhibitor of BTK, effectively blocking signaling and functional responses in both B cells and myeloid cells, and successfully inhibiting B-cell activation and antibody production in vivo.
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2021)
Article
Oncology
Hyori Kim, Mina Han, Minsong Kim, Hyeri Kim, Ho Joon Im, Nayoung Kim, Kyung-Nam Koh
Summary: The study developed anti-CD19/CD22 bispecific CAR structures using an anti-CD22 monoclonal antibody clone from chickens and analyzed their efficacy in human NK cell line NK-92 in vitro and in vivo. The results showed improved cytotoxicity against human B cell lymphoma cell line OCI-Ly7 compared to other CAR structures. This suggests that optimizing CAR structures in NK cells can enhance the efficacy of CAR therapy.
Article
Immunology
Pedram Mahmoudi Aliabadi, Khlowd Al-Qaisi, Peter K. K. Jani, Kazuhito Honjo, Uwe Klemm, Kyeong-Hee Lee, Nicole Baumgarth, Andreas Radbruch, Fritz Melchers, Hiromi Kubagawa
Summary: In previous studies, it was observed that Mott cells, a unique type of plasma cells containing Ig-inclusion bodies, were frequently found in peripheral lymphoid tissues of IgM Fc receptor (Fc mu R)-deficient (KO) mouse strain. By examining two additional mutant strains, it was confirmed that the enhanced Mott-cell formation was a general characteristic associated with Fc mu R deficiency. Further analysis revealed the regulatory role of Fc mu R in Mott cell and IgM-inclusion body formation.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Review
Immunology
Carlo Maria Rossi, Marco Vincenzo Lenti, Stefania Merli, Antonio Di Sabatino
Summary: IgM memory B cells may play a protective role against COVID-19 and other coronaviruses in the acute phase of infection, but further research is needed. Early detection of impaired IgM memory B cell response in patients can improve care and prognosis.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Gastroenterology & Hepatology
Takashi Nagaishi, Taro Watabe, Kunihiko Kotake, Toshihiko Kumazawa, Tomomi Aida, Kohichi Tanaka, Ryuichi Ono, Fumitoshi Ishino, Takako Usami, Takamasa Miura, Satomi Hirakata, Hiroko Kawasaki, Naoya Tsugawa, Daiki Yamada, Kazuhiro Hirayama, Soichiro Yoshikawa, Hajime Karasuyama, Ryuichi Okamoto, Mamoru Watanabe, Richard S. Blumberg, Takahiro Adachi
Summary: The study revealed that IgA plays a crucial role in mucosal homeostasis by regulating intestinal microbiota and protecting against mucosal inflammation, especially in the ileum. Mice lacking IgA showed spontaneous inflammation in the ileum and imbalanced intestinal microflora, while mice with IgA tail mutations appeared normal, suggesting the dispensability of the IgA cytoplasmic tail for preventing intestinal disorders.
Letter
Dermatology
Emi Kaneda, Kyoko Tonomura, Yorihisa Kotobuki, Ikuko Ueda-Hayakawa, Kanako Tasaka, Manabu Fujimoto
JOURNAL OF DERMATOLOGY
(2022)
Editorial Material
Dermatology
Tatsuya Ogawa, Yosuke Ishitsuka, Yoshiyuki Nakamura, Rei Watanabe, Naoko Okiyama, Yasuhiro Fujisawa, Manabu Fujimoto, Dennis R. Roop, Toshifumi Nomura
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Dermatology
Ryota Tanaka, Yuki Ichimura, Noriko Kubota, Risa Konishi, Yoshiyuki Nakamura, Seiya Mizuno, Satoru Takahashi, Manabu Fujimoto, Toshifumi Nomura, Naoko Okiyama
Summary: This study aimed to elucidate the regulatory role of LCs through the PD-1/PD-L1 axis and found that LCs disrupt the exacerbation of psoriasis through PD-L1.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Letter
Dermatology
Hanako Koguchi-Yoshioka, Hajime Nakano, Eijiro Akasaka, Atsushi Tanemura, Ichiro Katayama, Daisuke Sawamura, Manabu Fujimoto, Mari Wataya-Kaneda
JOURNAL OF DERMATOLOGY
(2022)
Article
Dermatology
Kazunori Yokoi, Noriko Arase, Takashi Shimbo, Manabu Fujimoto, Atsushi Tanemura
ACTA DERMATO-VENEREOLOGICA
(2023)
Letter
Dermatology
Yutaka Matsumura, Rei Watanabe, Hanako Koguchi-Yoshioka, Yuumi Nakamura, Aki Saito, Miki Kume, Shuichi Nakai, Yosuke Ishitsuka, Junichi Furuta, Manabu Fujimoto
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Dermatology
Yasushi Kikuchi, Tomoki Tamakoshi, Ryuichi Ishida, Ryosuke Kobayashi, Shiho Mori, Akemi Ishida-Yamamoto, Manabu Fujimoto, Yasufumi Kaneda, Katsuto Tamai
Summary: In this study, researchers developed an ex vivo gene therapy for recessive dystrophic epidermolysis bullosa (RDEB) using autologous mesenchymal stromal cells (MSCs). The gene-modified MSCs were injected into mice with type VII collagen deficiency, leading to continuous and widespread expression of type VII collagen. The therapy showed successful application in both early blistering skin and advanced ulcerative lesions in the RDEB mouse model.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Cell Biology
Shimpei Kawamoto, Ken Uemura, Nozomi Hori, Lena Takayasu, Yusuke Konishi, Kazutaka Katoh, Tomonori Matsumoto, Masae Suzuki, Yusuke Sakai, Tatsuyuki Matsudaira, Takahiro Adachi, Naoko Ohtani, Daron M. Standley, Wataru Suda, Shinji Fukuda, Eiji Hara
Summary: The mechanisms and control methods of ageing have been extensively studied. It has been discovered that the accumulation of senescent cells and the change in gut microbiota composition are two important factors in ageing. However, the relationship between these two phenomena during ageing is not well understood. In this study, researchers found that commensal bacteria gradually induce cellular senescence in gut germinal centre B cells, leading to reduced production and diversity of immunoglobulin A antibodies and changes in gut microbiota composition in aged mice. These findings reveal the existence of IgA-mediated crosstalk between gut microbiota and cellular senescence, providing insights into the mechanism of gut microbiota changes with age and potential strategies for control.
NATURE CELL BIOLOGY
(2023)
Article
Oncology
Kazunori Yokoi, Yoshiaki Yasumizu, Naganari Ohkura, Koei Shinzawa, Daisuke Okuzaki, Nene Shimoda, Hideya Ando, Nanako Yamada, Manabu Fujimoto, Atsushi Tanemura
Summary: In this study, it was found that the skin tightness of hypopigmented lesions in vitiligo patients was more evident compared to uninvolved perilesional skin. Collagen homeostasis in vitiligo lesions appeared to be maintained despite the excessive oxidative stress associated with the disease. The expression of collagen-related genes and anti-oxidative enzymes was upregulated, collagen degeneration was attenuated, and the NRF2 signaling pathway was activated in vitiligo dermis.
PIGMENT CELL & MELANOMA RESEARCH
(2023)
Editorial Material
Rheumatology
Manabu Fujimoto
ARTHRITIS & RHEUMATOLOGY
(2023)
Article
Dermatology
Mari Wataya-Kaneda, Shinichirou Maeda, Ayumi Nakamura, Misa Hayashi, Manabu Fujimoto
Summary: A pilot study was conducted to evaluate the safety and efficacy of 0.2% sirolimus gel for venous and capillary malformations, and to compare its efficacy with systemic sirolimus treatment. The results showed that the gel was as clinically effective as systemic treatment and more effective for early active lesions, even systemic venous malformations.
JOURNAL OF DERMATOLOGY
(2023)
Review
Immunology
Yutaka Matsumura, Rei Watanabe, Manabu Fujimoto
Summary: B cells, including regulatory B cells (Bregs), regulate inflammation through an inhibitory mechanism mediated by interleukin 10 (IL-10). Bregs have been reported in various disease models and play a role in autoimmune diseases, infectious diseases, cancer, and organ-transplant rejection. In addition to IL-10, other cytokines and membrane-binding molecules are also involved in the suppressive functions of Bregs. The identification and classification of Breg fractions remains challenging due to the variations in their activity and differentiation stages in different disease models.
INTERNATIONAL IMMUNOLOGY
(2023)
Article
Medicine, Research & Experimental
Yu Hirata, Kazuhiro Nomura, Daisuke Kato, Hiroaki Wake, Wataru Ogawa, Yu Hirata, Yoshihisa Tachibana, Takahiro Niikura, Kana Uchiyama, Tetsuya Hosooka, Tomoaki Fukui, Keisuke Oe, Ryosuke Kuroda, Yuji Hara, Takahiro Adachi, Koji Shibasaki
Summary: This study reveals that the upregulation of KLF15 and IL-6, as well as the decrease in intracellular Ca2+ concentration, are involved in muscle atrophy induced by immobility. This finding has been validated in both mouse models and human samples.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Immunology
Peng Gao, Takahiro Adachi, Shinsaku Okai, Naoki Morita, Daisuke Kitamura, Reiko Shinkura
Summary: CD11b(+)IgA(+) B cells may serve as precursors for entering germinal centers in murine Peyer's patches, and CD11b could be a potential marker for selecting effective mucosal vaccine adjuvants.
INTERNATIONAL IMMUNOLOGY
(2022)
