A Cre-deleter specific for embryo-derived brain macrophages reveals distinct features of microglia and border macrophages
Tools to target microglia specifically and efficiently from the embryonic development are lacking. Brioschi et  al. generated the Crybb1-Cre line, which recombines in microglia and border-associated macrophages during the embryonic stage. Combining Crybb1-Cre and other tools, they resolved embryonic-derived versus monocyte-derived BAMs in the mouse cortex. Deletion of the transcription SMAD4 using Crybb1-Cr e revealed that microglia require SMAD4 for differentiation. (Source: Immunity)
Source: Immunity - February 14, 2023 Category: Allergy & Immunology Authors: Simone Brioschi, Julia A. Belk, Vincent Peng, Martina Molgora, Patrick Fernandes Rodrigues, Khai M. Nguyen, Shoutang Wang, Siling Du, Wei-Le Wang, Gary E. Grajales-Reyes, Jennifer M. Ponce, Carla M. Yuede, Qingyun Li, John M. Baer, David G. DeNardo, Susan Tags: Article Source Type: research
Infection induces tissue-resident memory NK cells that safeguard tissue health
Immune activation can be damaging if responses are not adequately controlled. Schuster et  al. reveal that following cytomegalovirus infection, circulating natural killer cells are recruited into non-lymphoid tissues, including the salivary glands, where they establish a tissue-resident, memory-like population that prevents immune-mediated damage and safeguards tissue health by preventi ng autoimmunity. (Source: Immunity)
Source: Immunity - February 10, 2023 Category: Allergy & Immunology Authors: Iona S. Schuster, Xavier Y.X. Sng, Colleen M. Lau, David R. Powell, Orr-El Weizman, Peter Fleming, Georgia E.G. Neate, Valentina Voigt, Sam Sheppard, Andreas I. Maraskovsky, Sheridan Daly, Motoko Koyama, Geoffrey R. Hill, Stephen J. Turner, Timothy E. O â Tags: Article Source Type: research
Circumvention of luteolysis reveals parturition pathways in mice dependent upon innate type 2 immunity
Divergence across species in the endocrine control of labor onset has hindered our understanding of parturition mechanisms. Siewiera et  al. uncover a parturition-promoting role for innate type 2 immunity in mice when they are manipulated endocrinologically to resemble humans. (Source: Immunity)
Source: Immunity - February 6, 2023 Category: Allergy & Immunology Authors: Johan Siewiera, Tara I. McIntyre, Kelly M. Cautivo, Karim Mahiddine, Damon Rideaux, Ari B. Molofsky, Adrian Erlebacher Tags: Article Source Type: research
Single-cell and spatial transcriptomics reveal aberrant lymphoid developmental programs driving granuloma formation
Granulomas are accumulations of immune cells that help contain infections but can also give rise to diseases. To better understand granuloma formation, Krausgruber et  al. perform single-cell and spatial profiling of sarcoidosis-associated skin granulomas. They find that granulomas exploit molecular mechanisms underlying the formation of tertiary lymphoid structures but lack their overall control, indicating that granulomas constitute aberrant lymphoid organs. (Source: Immunity)
Source: Immunity - February 6, 2023 Category: Allergy & Immunology Authors: Thomas Krausgruber, Anna Redl, Daniele Barreca, Konstantin Doberer, Daria Romanovskaia, Lina Dobnikar, Maria Guarini, Luisa Unterluggauer, Lisa Kleissl, Denise Atzm üller, Carolina Mayerhofer, Aglaja Kopf, Simona Saluzzo, Clarice X. Lim, Praveen Rexie, T Tags: Article Source Type: research
Oxidative phosphorylation selectively orchestrates tissue macrophage homeostasis
Wculek et  al. uncover OXPHOS metabolism as a distinguishing feature among tissue macrophages in different organs in homeostasis. OXPHOS metabolism is required for maintenance of macrophage populations with high lipid- and cholesterol-handling activity. Thus, OXPHOS dysfunction impairs pro-inflammatory adipo se tissue macrophages in obesity, improving metabolic syndrome and hepatosteatosis. (Source: Immunity)
Source: Immunity - February 3, 2023 Category: Allergy & Immunology Authors: Stefanie K. Wculek, Ignacio Heras-Murillo, Annalaura Mastrangelo, Diego Ma ñanes, Miguel Galán, Verónica Miguel, Andrea Curtabbi, Coral Barbas, Navdeep S. Chandel, José Antonio EnrÃquez, Santiago Lamas, David Sancho Tags: Article Source Type: research
Ambient oxygen levels regulate intestinal dysbiosis and GVHD severity after allogeneic stem cell transplantation
Whether dysbiosis is a cause or consequence of pathology in intestinal diseases is not understood. Here, Seike et  al. show that defective oxygen utilization by intestinal epithelial cells leads to a loss of intestinal hypoxia and concomitant dysbiosis. Oxygen modulation rescues intestinal hypoxia and alleviates gastrointestinal graft-versus-host disease. (Source: Immunity)
Source: Immunity - February 2, 2023 Category: Allergy & Immunology Authors: Keisuke Seike, Anders Kiledal, Hideaki Fujiwara, Israel Henig, Marina Burgos da Silva, Marcel R.M. van den Brink, Robert Hein, Matthew Hoostal, Chen Liu, Katherine Oravecz-Wilson, Emma Lauder, Lu Li, Yaping Sun, Thomas M. Schmidt, Yatrik M. Shah, Robert R Tags: Article Source Type: research
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 Â cells to restrain DC1-mediated priming of cytotoxic TÂ 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 Â 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 Â 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 Â 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 Â 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
