Direct activation of microglia by β-glucosylceramide causes phagocytosis of neurons that exacerbates Gaucher disease
Gaucher disease is an inherited, incurable disorder with neuropathological complications caused by β-GlcCer accumulation, but its molecular action is unclear. Shimizu et al. show that β-GlcCer directly activates microglia to promote neuroinflammation leading to phagoptosis of living neurons and blockade of this pathway with FDA-approved drugs improves symptoms and survival. (Source: Immunity)
Source: Immunity - February 2, 2023 Category: Allergy & Immunology Authors: Takashi Shimizu, Charles R. Schutt, Yoshihiro Izumi, Noriyuki Tomiyasu, Zakaria Omahdi, Kuniyuki Kano, Hyota Takamatsu, Junken Aoki, Takeshi Bamba, Atsushi Kumanogoh, Masaki Takao, Sho Yamasaki Tags: Article Source Type: research
Tissue-specific abundance of interferon-gamma drives regulatory T cells to restrain DC1-mediated priming of cytotoxic T cells against lung cancer
How tissue-specific mechanisms shape anti-tumor immunity remains poorly understood. Zagorulya et al. reveal that lung lymph node (LN)-specific abundance of interferon-gamma induces suppressive Th1-like effector regulatory T (Treg) cells. These effector Treg cells interact with type 1 conventional dendritic cells and restrain priming of cytotoxic T cell responses against lung cancer. (Source: Immunity)
Source: Immunity - February 2, 2023 Category: Allergy & Immunology Authors: Maria Zagorulya, Leon Yim, Duncan M. Morgan, Austin Edwards, Elen Torres-Mejia, Noor Momin, Chloe V. McCreery, Izabella L. Zamora, Brendan L. Horton, James G. Fox, K. Dane Wittrup, J. Christopher Love, Stefani Spranger Tags: Article Source Type: research
Spermine enhances antiviral and anticancer responses by stabilizing DNA binding with the DNA sensor cGAS
Self-nonself discrimination is central to effective immunity, but how intracellular DNA is discriminated remains elusive. Here, Wang et al. show that spermine condenses naked DNA (including viral DNA) but not nucleosomal DNA to promote cGAS binding and downstream immune activation, thus providing a mechanism for self-nonself recognition. (Source: Immunity)
Source: Immunity - January 31, 2023 Category: Allergy & Immunology Authors: Lina Wang, Siru Li, Kai Wang, Na Wang, Qiaoling Liu, Zhen Sun, Li Wang, Lulu Wang, Quentin Liu, Chengli Song, Qingkai Yang Tags: Article Source Type: research
The landscape of immune dysregulation in Crohn ’s disease revealed through single-cell transcriptomic profiling in the ileum and colon
Crohn ’s disease (CD) is a heterogeneous condition impacting the ileum and colon in unique ways. Here, Kong et al. define the unique epithelial, stromal, and immune characteristics of CD by generating a single-cell transcriptomic atlas of the ileum and colon and uncover novel regulators of collagen pro duction in disease-associated fibroblasts. (Source: Immunity)
Source: Immunity - January 30, 2023 Category: Allergy & Immunology Authors: Lingjia Kong, Vladislav Pokatayev, Ariel Lefkovith, Grace T. Carter, Elizabeth A. Creasey, Chirag Krishna, Sathish Subramanian, Bharati Kochar, Orr Ashenberg, Helena Lau, Ashwin N. Ananthakrishnan, Daniel B. Graham, Jacques Deguine, Ramnik J. Xavier Tags: Resource Source Type: research
Graft-versus-host disease is locally maintained in target tissues by resident progenitor-like T cells
Alloreactive T cells cause graft-versus-host disease (GVHD), but how GVHD is maintained once established is unclear. Using T cell clone tracking, parabiosis of GVHD mice and computational modeling, Sacirbegovic et al. demonstrate that progenitor-like T cells within affected tissues maintain GVHD locally, most ly independent of blood-derived T cells. (Source: Immunity)
Source: Immunity - January 30, 2023 Category: Allergy & Immunology Authors: Faruk Sacirbegovic, Matthias G ünther, Alessandro Greco, Daqiang Zhao, Xi Wang, Meng Zhou, Sarah Rosenberger, Martin H. Oberbarnscheidt, Werner Held, Jennifer McNiff, Dhanpat Jain, Thomas Höfer, Warren D. Shlomchik Tags: Article Source Type: research
Dopamine inhibits group 2 innate lymphoid cell-driven allergic lung inflammation by dampening mitochondrial activity
Neuroimmune interactions play an emerging role in the regulation of ILC2 and allergic inflammation, but the underlying mechanism remains to be fully understood. Cao et al. report that dopamine constrains ILC2 responses and alleviates allergic airway inflammation via DRD1 receptor. (Source: Immunity)
Source: Immunity - January 23, 2023 Category: Allergy & Immunology Authors: Yingjiao Cao, Yu Li, Xiangyang Wang, Shaorui Liu, Yongmei Zhang, Gaoyu Liu, Shusen Ye, Yuhao Zheng, Jiacong Zhao, Xiaodong Zhu, Yingying Chen, Haixu Xu, Dingyun Feng, Dubo Chen, Ling Chen, Wangkai Liu, Wenjie Zhou, Zhi Zhang, Pan Zhou, Kai Deng, Lilin Ye, Tags: Article Source Type: research
CD8+ T cell activation in cancer comprises an initial activation phase in lymph nodes followed by effector differentiation within the tumor
Better understanding of the fundamental mechanisms controlling anti-tumor T cell responses is needed. Here, Prokhnevska et al. describe a two-step T cell activation response to cancer: (1) initial priming in tumor-draining lymph nodes resulting in a stem-like phenotype and (2) a co-stimulation-dependent phase in the tumor to acquire effector programming. (Source: Immunity)
Source: Immunity - December 28, 2022 Category: Allergy & Immunology Authors: Nataliya Prokhnevska, Maria A. Cardenas, Rajesh M. Valanparambil, Ewelina Sobierajska, Benjamin G. Barwick, Caroline Jansen, Adriana Reyes Moon, Petra Gregorova, Luke delBalzo, Rachel Greenwald, Mehmet Asim Bilen, Mehrdad Alemozaffar, Shreyas Joshi, Cara Tags: Article Source Type: research
Small intestine and colon tissue-resident memory CD8+ T cells exhibit molecular heterogeneity and differential dependence on Eomes
The tissue- and context-specific regulation of tissue-resident memory T (TRM) cells, which provide protection in organs and at barrier sites, is an emerging concept. Lin et al. show that CD8+ TRM cells from the SI vs. the colon exhibit unique molecular and functional attributes along with distinct transcriptional requirements for their maintenance. (Source: Immunity)
Source: Immunity - December 28, 2022 Category: Allergy & Immunology Authors: Yun Hsuan Lin, Han G. Duong, Abigail E. Limary, Eleanor S. Kim, Paul Hsu, Shefali A. Patel, William H. Wong, Cynthia S. Indralingam, Yi Chia Liu, Priscilla Yao, Natalie R. Chiang, Sara A. Vandenburgh, Taylor R. Anderson, Jocelyn G. Olvera, Amir Ferry, Ken Tags: Resource Source Type: research
The ectonucleotidase CD39 identifies tumor-reactive CD8+ T cells predictive of immune checkpoint blockade efficacy in human lung cancer
Factors predicting benefit of immune checkpoint blockade (ICB) are needed. Here, Chow et al. demonstrate that CD39 expression marks tumor-reactive CD8+ T cells. High baseline levels of CD39+ CD8+ T cells are associated with ICB efficacy in lung cancer. Thus, CD39 is a potential tumor-extrinsic biomarker for guiding cancer management. (Source: Immunity)
Source: Immunity - December 26, 2022 Category: Allergy & Immunology Authors: Andrew Chow, Fathema Z. Uddin, Michael Liu, Anton Dobrin, Barzin Y. Nabet, Levi Mangarin, Yonit Lavin, Hira Rizvi, Sam E. Tischfield, Alvaro Quintanal-Villalonga, Joseph M. Chan, Nisargbhai Shah, Viola Allaj, Parvathy Manoj, Marissa Mattar, Maximiliano Me Tags: Article Source Type: research
Immune checkpoint therapy-elicited sialylation of IgG antibodies impairs antitumorigenic type I interferon responses in hepatocellular carcinoma
Although immune checkpoint blockade (ICB) influence on T cells is well known, its impact on antibodies is less understood. Wu et al. show how ICB-elicited sialylation of IgG suppresses DC-SIGN-expressing macrophages in human hepatocellular carcinoma. Impeding IgG sialylation augments macrophage IFN-I responses and antitumorigenic T cell immunity durin g immunotherapy. (Source: Immunity)
Source: Immunity - December 22, 2022 Category: Allergy & Immunology Authors: Rui-Qi Wu, Xiang-Ming Lao, Dong-Ping Chen, Hongqiang Qin, Ming Mu, Wen-Jie Cao, Jia Deng, Chao-Chao Wan, Wan-Yu Zhan, Jun-Cheng Wang, Li Xu, Min-Shan Chen, Qiang Gao, Limin Zheng, Yuan Wei, Dong-Ming Kuang Tags: Article Source Type: research
Prolonged hypernutrition impairs TREM2-dependent efferocytosis to license chronic liver inflammation and NASH development
Obesity-induced chronic liver inflammation drives nonalcoholic steatohepatitis (NASH) development; however, it remains unclear how such a low-grade inflammation is sustained in the liver. Wang et al. now show that prolonged hypernutrition dismantles TREM2-dependent macrophage efferocytosis of lipid-laden apoptotic hepatocytes, resulting in their aberrant accumulation to precipitate chronic liver inflammation and NASH progression. (Source: Immunity)
Source: Immunity - December 14, 2022 Category: Allergy & Immunology Authors: Xiaochen Wang, Qifeng He, Chuanli Zhou, Yueyuan Xu, Danhui Liu, Naoto Fujiwara, Naoto Kubota, Arielle Click, Polly Henderson, Janiece Vancil, Cesia Ammi Marquez, Ganesh Gunasekaran, Myron E. Schwartz, Parissa Tabrizian, Umut Sarpel, Maria Isabel Fiel, Yar Tags: Article Source Type: research
Immunoglobulin germline gene polymorphisms influence the function of SARS-CoV-2 neutralizing antibodies
The genes and alleles of the antigen receptor loci are highly variable between individuals, which may affect the quality of the immune response to different pathogens. Here, Pushparaj et. al. use immunoglobulin genotyping and monoclonal antibody engineering to illustrate how heritable differences in such genes can modulate anti-SARS-CoV-2 antibody function. (Source: Immunity)
Source: Immunity - December 11, 2022 Category: Allergy & Immunology Authors: Pradeepa Pushparaj, Andrea Nicoletto, Daniel J. Sheward, Hrishikesh Das, Xaquin Castro Dopico, Laura Perez Vidakovics, Leo Hanke, Mark Chernyshev, Sanjana Narang, Sungyong Kim, Julian Fischbach, Simon Ekstr öm, Gerald McInerney, B. Martin Hällberg, Ben Tags: Article Source Type: research
Gut microbiota promotes stem cell differentiation through macrophage and mesenchymal niches in early postnatal development
Intestinal development coincides with microbial exposure after birth, but how they influence each other is unresolved. Here, Kim et al. report that postnatal gut microbiota promote stem cell differentiation through regulation of a macrophage and mesenchymal niche. This niche is disrupted by antibiotics but can be partially rescued by Lactobacillus. (Source: Immunity)
Source: Immunity - December 5, 2022 Category: Allergy & Immunology Authors: Ji-Eun Kim, Bo Li, Lijiang Fei, Rachael Horne, Dorothy Lee, Adrian Kwan Loe, Hiromu Miyake, Eda Ayar, Dae-Kyum Kim, Michael G. Surette, Dana J. Philpott, Philip Sherman, Guoji Guo, Agostino Pierro, Tae-Hee Kim Tags: Article Source Type: research
Allergenic food protein consumption is associated with systemic IgG antibody responses in non-allergic individuals
Adults ingest approximately 2 kg of food per day, which can exert a variety of effects on the immune system. Leviatan et al. studied population-scale antibody responses against food and environmental antigens combined from different databases using PhIP-seq. They identified IgG antibodies in the blood of non-allergic adults t argeting food proteins that were associated with health parameters, such as diet. (Source: Immunity)
Source: Immunity - December 5, 2022 Category: Allergy & Immunology Authors: Sigal Leviatan, Thomas Vogl, Shelley Klompus, Iris N. Kalka, Adina Weinberger, Eran Segal Tags: Resource Source Type: research
B cell expansion hinders the stroma-epithelium regenerative cross talk during mucosal healing
The cellular mechanisms controlling mucosal healing (MH) following injury are largely unknown. Using unbiased multi-parameter analysis, Frede and colleagues identified that B cells accumulate in the colonic damaged areas during MH. Surprisingly, B cells played detrimental roles during MH, as their presence hindered the interaction between epithelium and stroma. (Source: Immunity)
Source: Immunity - December 2, 2022 Category: Allergy & Immunology Authors: Annika Frede, Paulo Czarnewski, Gustavo Monasterio, Kumar P. Tripathi, David A. Bejarano, Ricardo O. Ramirez Flores, Chiara Sorini, Ludvig Larsson, Xinxin Luo, Laura Geerlings, Claudio Novella-Rausell, Chiara Zagami, Raoul Kuiper, Rodrigo A. Morales, Fran Tags: Article Source Type: research
