Ketolysis drives CD8+ T cell effector function through effects on histone acetylation
Environmental nutrient availability influences T cell function, yet the substrates that fuel T cell metabolism in vivo are poorly defined. Here, Luda and Longo et al. identify ketolysis (breakdown of ketone bodies) as a metabolic pathway required for optimal CD8+ T cell effector function in vivo. Ketone bodies, including βOHB, are physiolo gic fuels for T cells, preferred over glucose for acetyl-CoA synthesis, and regulate effector function through effects on histone acetylation. (Source: Immunity)
Source: Immunity - July 28, 2023 Category: Allergy & Immunology Authors: Katarzyna M. Luda, Joseph Longo, Susan M. Kitchen-Goosen, Lauren R. Duimstra, Eric H. Ma, McLane J. Watson, Brandon M. Oswald, Zhen Fu, Zachary Madaj, Ariana Kupai, Bradley M. Dickson, Lisa M. DeCamp, Michael S. Dahabieh, Shelby E. Compton, Robert Teis, I Tags: Article Source Type: research
Dendritic cell type 3 arises from Ly6C+ monocyte-dendritic cell progenitors
Delineating the lineage development of dendritic cells (DCs) is challenging as these cells show overlapping phenotypes with monocytes and other cells. Using single-cell sequencing and fate mapping approaches, Liu et al. demonstrate that murine DCs develop through three lineages, with DC3s developing from Ly6C+ monocyte-dendritic cell progenitors (MDPs) through pro-DC3s. (Source: Immunity)
Source: Immunity - July 27, 2023 Category: Allergy & Immunology Authors: Zhaoyuan Liu, Haiting Wang, Ziyi Li, Regine J. Dress, Yiwen Zhu, Shuangyan Zhang, Donatella De Feo, Wan Ting Kong, Peiliang Cai, Amanda Shin, C écile Piot, Jiangyan Yu, Yaqi Gu, Mingnan Zhang, Caixia Gao, Lei Chen, Honglin Wang, Mathias Vétillard, Pierr Tags: Article Source Type: research
Human anti-N1 monoclonal antibodies elicited by pandemic H1N1 virus infection broadly inhibit HxN1 viruses in vitro and in vivo
Optimizing neuraminidase antigenicity is essential for improving influenza vaccines. Hansen et al. isolated human monoclonal antibodies with broad enzyme inhibition activity against human, avian, and swine N1 neuraminidase that provided robust protection in vivo. Cryo-EM revealed highly conserved sites on the lateral face of neuraminidase, distal to the active site. (Source: Immunity)
Source: Immunity - July 27, 2023 Category: Allergy & Immunology Authors: Lena Hansen, Meagan McMahon, Hannah L. Turner, Xueyong Zhu, Jackson S. Turner, Gabriel Ozorowski, Daniel Stadlbauer, Juha Vahokoski, Aaron J. Schmitz, Amena A. Rizk, Wafaa B. Alsoussi, Shirin Strohmeier, Wenli Yu, Jos é Alberto Choreño-Parra, Luis Jimé Tags: Article Source Type: research
Cell-autonomous regulation of complement C3 by factor H limits macrophage efferocytosis and exacerbates atherosclerosis
Misregulation of complement cascade is associated with chronic inflammatory disease. Kiss et al. report the impact of local complement regulation on atherosclerotic lesions, finding that monocyte-derived complement factor H limits cell-autonomous alternative complement activation. This regulation restricts monocyte-derived macrophages’ pro-resolving functions and promotes plaque necrosi s in a murine model of atherosclerosis. (Source: Immunity)
Source: Immunity - July 26, 2023 Category: Allergy & Immunology Authors: M áté G. Kiss, Nikolina Papac-Miličević, Florentina Porsch, Dimitrios Tsiantoulas, Tim Hendrikx, Minoru Takaoka, Huy Q. Dinh, Marie-Sophie Narzt, Laura Göderle, Mária Ozsvár-Kozma, Michael Schuster, Nikolaus Fortelny, Anastasiya Hladik, Sylvia Knap Tags: Article Source Type: research
Graded expression of the chemokine receptor CX3CR1 marks differentiation states of human and murine T cells and enables cross-species interpretation
Differentiation states are delineated by different cell surface markers for murine and human T cells, which hamper cross-species translation of T cell properties. Zwijnenburg et al. demonstrate that the graded expression of the chemokine receptor CX3CR1 reflects the T cell differentiation spectrum in humans and mice, providing a practical strategy to translate the behavior of distinct T cell states across species. (Source: Immunity)
Source: Immunity - July 24, 2023 Category: Allergy & Immunology Authors: Anthonie Johan Zwijnenburg, Jyoti Pokharel, Renata Varnait ė, Wenning Zheng, Elena Hoffer, Iman Shryki, Natalia Ramirez Comet, Marcus Ehrström, Sara Gredmark-Russ, Liv Eidsmo, Carmen Gerlach Tags: Resource Source Type: research
Intestinal microbiota controls graft-versus-host disease independent of donor-host genetic disparity
Genetically identical recipient and donor pairs are associated with differential MHC-II expression on intestinal epithelial cells (IECs) and subsequent graft-versus-host disease, which is controlled by the composition of commensal bacteria. Koyama et al. identify taxa that positively (inducers) and negatively (suppressors) correlate with MHC-II expression on IECs and show that this is regulated by IFNγ-secreting intestinal T cells. (Source: Immunity)
Source: Immunity - July 21, 2023 Category: Allergy & Immunology Authors: Motoko Koyama, Daniel S. Hippe, Sujatha Srinivasan, Sean C. Proll, Oriana Miltiadous, Naisi Li, Ping Zhang, Kathleen S. Ensbey, Noah G. Hoffman, Christine R. Schmidt, Albert C. Yeh, Simone A. Minnie, Susan M. Strenk, Tina L. Fiedler, Namita Hattangady, Ja Tags: Article Source Type: research
Influenza vaccine format mediates distinct cellular and antibody responses in human immune organoids
Understanding the cellular dynamics underlying responses to different antigen formats is critical for rational vaccine design. Using a human immune organoid model, Kastenschmidt et al. evaluate the effect of influenza vaccine modalities on adaptive immunity and reveal key differences in the magnitude, breadth, and quality of B cell, T cell, and antibody responses. (Source: Immunity)
Source: Immunity - July 20, 2023 Category: Allergy & Immunology Authors: Jenna M. Kastenschmidt, Suhas Sureshchandra, Aarti Jain, Jenny E. Hernandez-Davies, Rafael de Assis, Zachary W. Wagoner, Andrew M. Sorn, Mahina Tabassum Mitul, Aviv I. Benchorin, Elizabeth Levendosky, Gurpreet Ahuja, Qiu Zhong, Douglas Trask, Jacob Boeckm Tags: Article Source Type: research
Obesity-induced dysregulation of skin-resident PPAR γ+ Treg cells promotes IL-17A-mediated psoriatic inflammation
Obesity is a major risk factor for inflammatory skin diseases, in particular psoriasis. Sivasami et al. demonstrate that diet-induced obesity dysregulates a distinct subset of PPARγ+ Tregs in the skin via fatty-acid-induced lipotoxicity, which results in loss of control over IL-17A+ γδ T cell-mediated inflammation and exacerbated psoriasis. (Source: Immunity)
Source: Immunity - July 20, 2023 Category: Allergy & Immunology Authors: Pulavendran Sivasami, Cody Elkins, Pamela P. Diaz-Saldana, Kyndal Goss, Amy Peng, Michael Hamersky, Jennifer Bae, Miaoer Xu, Brian P. Pollack, Edwin M. Horwitz, Christopher D. Scharer, Lindsey Seldin, Chaoran Li Tags: Article Source Type: research
The gut protist Tritrichomonas arnold restrains virus-mediated loss of oral tolerance by modulating dietary antigen-presenting dendritic cells
Enteric viruses can trigger loss of oral tolerance to dietary gluten, resulting in the development of celiac disease. Medina Sanchez et al. discovered Tritrichomonas arnold, a previously undescribed murine gut commensal protist capable of preventing virus-mediated loss of oral tolerance by directly restraining proinflammatory dendritic cell function. (Source: Immunity)
Source: Immunity - July 20, 2023 Category: Allergy & Immunology Authors: Luzmariel Medina Sanchez, Magdalena Siller, Yanlin Zeng, Pamela H. Brigleb, Kishan A. Sangani, Ariadna S. Soto, Clarisse Engl, Colin R. Laughlin, Mohit Rana, Lauren Van Der Kraak, Surya P. Pandey, Mackenzie J. Bender, Britney Fitzgerald, Lee Hedden, Kay F Tags: Article Source Type: research
Targeted removal of macrophage-secreted interleukin-1 receptor antagonist protects against lethal Candida albicans sepsis
Invasive candidiasis has high mortality rates with limited therapeutic options. Gander-Bui et al. show how macrophage-secreted IL-1 receptor antagonist (IL-1Ra) restricts recruitment of fungicidal neutrophils and drives candidiasis pathology. Therapeutic IL-1Ra neutralization protects against lethal Candida sepsis; however, interferon-driven amplification of IL-1Ra during viral infection e xacerbates fungal dissemination and disease. (Source: Immunity)
Source: Immunity - July 20, 2023 Category: Allergy & Immunology Authors: Hang Thi Thuy Gander-Bui, Jo ëlle Schläfli, Johanna Baumgartner, Sabrina Walthert, Vera Genitsch, Geert van Geest, José A. Galván, Carmen Cardozo, Cristina Graham Martinez, Mona Grans, Sabine Muth, Rémy Bruggmann, Hans Christian Probst, Cem Gabay, St Tags: Article Source Type: research
An autonomous activation of interleukin-17 receptor signaling sustains inflammation and promotes disease progression
The efficacy of anti-IL-17 therapy for various IL-17-related diseases is unexpectedly limited for unknown reasons. Luo et al. reveal an IL-17-established mechanism consisting of Act1-SHP2 complex that primes autonomous activation of IL-17R signaling in a ligand-independent manner, sustains inflammation, thereby invalidating the efficacy of anti-IL-17 therapy. (Source: Immunity)
Source: Immunity - July 19, 2023 Category: Allergy & Immunology Authors: Qiong Luo, Yijun Liu, Ke Shi, Xuecheng Shen, Yaqi Yang, Xuejiao Liang, Liangliang Lu, Wenxuan Qiao, Airu Chen, Dongmei Hong, Yang Sun, Qiang Xu Tags: Article Source Type: research
Lymph node medulla regulates the spatiotemporal unfolding of resident dendritic cell networks
Conventional dendritic cells (cDCs) are short-lived cells, being constantly replaced by precursors (preDCs) from the bone marrow. Ugur et al. provide insight into the niches that maintain these cells, showing that preDCs home to the LN medulla and generate a network that extends toward the paracortex. Inflammation promotes rapid maturation of cDC1s, leaving gaps in this network that are filled by local Flt3L feedback. (Source: Immunity)
Source: Immunity - July 17, 2023 Category: Allergy & Immunology Authors: Milas Ugur, R. Jacob Labios, Chloe Fenton, Konrad Kn öpper, Katarzyna Jobin, Fabian Imdahl, Gosia Golda, Kathrin Hoh, Anika Grafen, Tsuneyasu Kaisho, Antoine-Emmanuel Saliba, Dominic Grün, Georg Gasteiger, Marc Bajénoff, Wolfgang Kastenmüller Tags: Article Source Type: research
Hypoxic niches attract and sequester tumor-associated macrophages and cytotoxic T cells and reprogram them for immunosuppression
Glioblastoma is notorious for immunosuppression, but the mechanisms are unclear. Sattiraju et al. report that hypoxic zones in GBM attract and sequester tumor-associated myeloid cells and cytotoxic T cells, where they are reprogrammed into an immunosuppressive state. This process is influenced by the immunocompetence state of the host and involves CCL8 and IL-1B as niche factors in hypoxi c zones. (Source: Immunity)
Source: Immunity - July 13, 2023 Category: Allergy & Immunology Authors: Anirudh Sattiraju, Sangjo Kang, Bruno Giotti, Zhihong Chen, Valerie J. Marallano, Concetta Brusco, Aarthi Ramakrishnan, Li Shen, Alexander M. Tsankov, Dolores Hambardzumyan, Roland H. Friedel, Hongyan Zou Tags: Article Source Type: research
Expression of the readthrough transcript CiDRE in alveolar macrophages boosts SARS-CoV-2 susceptibility and promotes COVID-19 severity
Elucidating the mechanism underlying COVID-19 severity is essential for individualized therapy. Mitsui et al. demonstrate that IL-10 induces ACE2 expression in alveolar macrophages and promotes COVID-19 severity. Individuals harboring COVID-19 risk variants at the IFNAR2-IL10RB locus exhibit augmented expression of the hybrid receptor, CiDRE, on these macrophages, thereby heightening their sensitivity to IL-10. (Source: Immunity)
Source: Immunity - July 12, 2023 Category: Allergy & Immunology Authors: Yuichi Mitsui, Tatsuya Suzuki, Kanako Kuniyoshi, Jun Inamo, Kensuke Yamaguchi, Mariko Komuro, Junya Watanabe, Mio Edamoto, Songling Li, Tsukasa Kouno, Seiya Oba, Tadashi Hosoya, Kentaro Masuhiro, Yujiro Naito, Shohei Koyama, Nobuo Sakaguchi, Daron M. Stan Tags: Article Source Type: research
TREM2 receptor protects against complement-mediated synaptic loss by binding to complement C1q during neurodegeneration
TREM2 is strongly linked to Alzheimer ’s disease risk, but its functions are not fully understood. Zhong et al. discovered that TREM2 suppresses complement activity and synaptic loss by binding to C1q. They identified a 41-amino-acid TREM2 peptide that restricts complement-mediated synaptic elimination during neurodegeneration. (Source: Immunity)
Source: Immunity - July 12, 2023 Category: Allergy & Immunology Authors: Li Zhong, Xuan Sheng, Wanbing Wang, Yanzhong Li, Rengong Zhuo, Kai Wang, Lianshuai Zhang, Dan-Dan Hu, Yujuan Hong, Linting Chen, Hengjun Rao, Tingting Li, Muyang Chen, Zhihao Lin, Yun-wu Zhang, Xin Wang, Xiao-Xin Yan, Xiaochun Chen, Guojun Bu, Xiao-Fen Ch Tags: Article Source Type: research
