Dual ontogeny of disease-associated microglia and disease inflammatory macrophages in aging and neurodegeneration
Through 6 scRNA-seq brain dataset integration, the authors generated a myeloid map called M-Verse to delineate macrophage population heterogeneity. M-Verse revealed two distinct macrophage populations expressing published disease-associated microglia (DAM) signature: embryonically derived TREM2-dependent DAM and monocyte-derived TREM2-independent disease inflammatory macrophages (DIMs). (Source: Immunity)
Source: Immunity - August 4, 2022 Category: Allergy & Immunology Authors: Aymeric Silvin, Stefan Uderhardt, Cecile Piot, Sandro Da Mesquita, Katharine Yang, Laufey Geirsdottir, Kevin Mulder, David Eyal, Zhaoyuan Liu, Cecile Bridlance, Morgane Sonia Thion, Xiao Meng Zhang, Wan Ting Kong, Marc Deloger, Vasco Fontes, Assaf Weiner, Tags: Article Source Type: research
Antibodies from primary humoral responses modulate recruitment of naive B cells during secondary responses
Using preclinical models for HIV and SARS-CoV, Tas et al. show that circulating antibodies from primary responses affect which na ïve B cells participate in germinal centers after secondary challenges. The directionality and intensity of this influence is determined by the epitope-specificity of the primary response, and by the affinity and concentration of the circulating antibody. (Source: Immunity)
Source: Immunity - August 4, 2022 Category: Allergy & Immunology Authors: Jeroen M.J. Tas, Ja-Hyun Koo, Ying-Cing Lin, Zhenfei Xie, Jon M. Steichen, Abigail M. Jackson, Blake M. Hauser, Xuesong Wang, Christopher A. Cottrell, Jonathan L. Torres, John E. Warner, Kathrin H. Kirsch, Stephanie R. Weldon, Bettina Groshel, Bartek Noga Tags: Article Source Type: research
The transcription factor FoxP3 can fold into two dimerization states with divergent implications for regulatory T cell function and immune homeostasis
FoxP3 is an essential transcription factor for regulatory T cells and overall immunologic homeostasis. We show that the forkhead DNA-binding domains of FoxP3 form a unique head-to-head dimer. This is important for DNA and cofactor binding and provides functional specificity. Furthermore, a disease mutation inducing alternative dimerization impairs Foxp3 fu nction. (Source: Immunity)
Source: Immunity - August 3, 2022 Category: Allergy & Immunology Authors: Fangwei Leng, Wenxiang Zhang, Ricardo N. Ramirez, Juliette Leon, Yi Zhong, Lifei Hou, Koichi Yuki, Joris van der Veeken, Alexander Y. Rudensky, Christophe Benoist, Sun Hur Tags: Article Source Type: research
Lung fibroblasts facilitate pre-metastatic niche formation by remodeling the local immune microenvironment
Improved understanding of how the lung stroma contributes to the development of an immunosuppressive pre-metastatic niche could potentiate new anti-cancer treatments. Here, Gong et al. identify COX-2+ lung fibroblasts that reprogram diverse myeloid cells to be dysfunctional or immunosuppressive. Targeting COX-2+ AdvFs reduced lung metastasis and improved efficacy of immunotherapeutics. (Source: Immunity)
Source: Immunity - July 30, 2022 Category: Allergy & Immunology Authors: Zheng Gong, Qing Li, Jiayuan Shi, Jian Wei, Peishan Li, Chih-Hao Chang, Leonard D. Shultz, Guangwen Ren Tags: Article Source Type: research
Interleukin-21, acting beyond the immunological synapse, independently controls T follicular helper and germinal center B cells
The formation and maintenance of germinal centers is fundamental to humoral immunity and requires interleukin 21 (IL-21). Quast et al. show that IL-21 independently regulates germinal center T and B cells and that its effects occur in paracrine, related to amount and outside the confines of the T-B synapse. (Source: Immunity)
Source: Immunity - July 26, 2022 Category: Allergy & Immunology Authors: Isaak Quast, Alexandra R. Dvorscek, Celine Pattaroni, Thiago M. Steiner, Craig I. McKenzie, Catherine Pitt, Kristy O ’Donnell, Zhoujie Ding, Danika L. Hill, Robert Brink, Marcus J. Robinson, Dimitra Zotos, David M. Tarlinton Tags: Article Source Type: research
Transcription factors TCF-1 and GATA3 are key factors for the epigenetic priming of early innate lymphoid progenitors toward distinct cell fates
EILPs have multiple lineage potentials toward either myeloid or ILC lineages, but the role of epigenetic modifications in the cell-fate decision is presently unclear. Ren et al. reveal that EILPs contain distinct epigenetically primed subpopulations, which are dependent on the presence of transcription factors TCF-1 and GATA3. (Source: Immunity)
Source: Immunity - July 25, 2022 Category: Allergy & Immunology Authors: Gang Ren, Binbin Lai, Christelle Harly, Songjoon Baek, Yi Ding, Mingzhu Zheng, Yaqiang Cao, Kairong Cui, Yu Yang, Jinfang Zhu, Gordon L. Hager, Avinash Bhandoola, Keji Zhao Tags: Article Source Type: research
Keratinocyte-derived defensins activate neutrophil-specific receptors Mrgpra2a/b to prevent skin dysbiosis and bacterial infection
Antimicrobial peptides (AMPs) are vital for host defense. Dong et al. discover that keratinocyte-derived defensins activate G-protein-coupled receptors Mrgpra2a/b on neutrophils. This epithelial-neutrophil signaling axis prevents skin dysbiosis and is required for immunity against bacterial infections. (Source: Immunity)
Source: Immunity - July 25, 2022 Category: Allergy & Immunology Authors: Xintong Dong, Nathachit Limjunyawong, Elizabeth I. Sypek, Gaofeng Wang, Roger V. Ortines, Christine Youn, Martin P. Alphonse, Dustin Dikeman, Yu Wang, Mark Lay, Ruchita Kothari, Chirag Vasavda, Priyanka Pundir, Loyal Goff, Lloyd S. Miller, Wuyuan Lu, Luis Tags: Article Source Type: research
Microglia-derived PDGFB promotes neuronal potassium currents to suppress basal sympathetic tonicity and limit hypertension
The local, non-synaptic mechanisms that determine neuronal excitability remain unclear. Bi et al. find that microglia prevent sympathetic overactivation via constitutively releasing PDGFB, which promotes the expression of the potassium channel Kv4.3 in pre-sympathetic neurons of the hypothalamic paraventricular nucleus. These findings show that microglia play an important role in maintaini ng the homeostasis of neuronal excitability and peripheral autonomic functions. (Source: Immunity)
Source: Immunity - July 20, 2022 Category: Allergy & Immunology Authors: Qianqian Bi, Chao Wang, Guo Cheng, Ningting Chen, Bo Wei, Xiaoli Liu, Li Li, Cheng Lu, Jian He, Yuancheng Weng, Chunyou Yin, Yunfan Lin, Shu Wan, Li Zhao, Jiaxi Xu, Yi Wang, Yan Gu, Xiao Z. Shen, Peng Shi Tags: Article Source Type: research
Immunodeficiency syndromes differentially impact the functional profile of SARS-CoV-2-specific T cells elicited by mRNA vaccination
Many immunocompromised individuals respond poorly to mRNA vaccination and are at higher risk of developing severe COVID-19. Gao and Cai et al. provide the single-cell landscape of SARS-CoV-2-specific T cells after mRNA vaccination and observe that the functional quality of memory T cell responses varies considerably across different immunodeficiency syndromes. (Source: Immunity)
Source: Immunity - July 18, 2022 Category: Allergy & Immunology Authors: Yu Gao, Curtis Cai, David Wullimann, Julia Niessl, Olga Rivera-Ballesteros, Puran Chen, Joshua Lange, Angelica Cuapio, Ola Blennow, Lotta Hansson, Stephan Mielke, Piotr Nowak, Jan Vesterbacka, Mira Akber, Andre Perez-Potti, Takuya Sekine, Thomas R. M üll Tags: Article Source Type: research
Immunodeficiency syndromes differentially impact the functional spectrum of SARS-CoV-2-specific T cells elicited by mRNA vaccination
Many immunocompromised individuals respond poorly to mRNA vaccination and are at higher risk of developing severe COVID-19. Gao and Cai et al. provide the single-cell landscape of SARS-CoV-2-specific T cells after mRNA vaccination and observe that the functional quality of memory T cell responses varies considerably across different immunodeficiency syndromes. (Source: Immunity)
Source: Immunity - July 18, 2022 Category: Allergy & Immunology Authors: Yu Gao, Curtis Cai, David Wullimann, Julia Niessl, Olga Rivera-Ballesteros, Puran Chen, Joshua Lange, Angelica Cuapio, Ola Blennow, Lotta Hansson, Stephan Mielke, Piotr Nowak, Jan Vesterbacka, Mira Akber, Andre Perez-Potti, Takuya Sekine, Thomas R. M üll Tags: Article Source Type: research
Oxidized DNA fragments exit mitochondria via mPTP- and VDAC-dependent channels to activate NLRP3 inflammasome and interferon signaling
Ox-mtDNA enables NLRP3 inflammasome activation, but how Ox-mtDNA reaches the cytoplasm is unclear. In this issue of Immunity, Xian et al. show that Ox-mtDNA cleaved by FEN1 escapes mitochondria via mPTP and VDAC channels to activate NLRP3 inflammasome and STING. (Source: Immunity)
Source: Immunity - July 13, 2022 Category: Allergy & Immunology Authors: Hongxu Xian, Kosuke Watari, Elsa Sanchez-Lopez, Joseph Offenberger, Janset Onyuru, Harini Sampath, Wei Ying, Hal M. Hoffman, Gerald S. Shadel, Michael Karin Tags: Article Source Type: research
IRF8 deficiency induces the transcriptional, functional, and epigenetic reprogramming of cDC1 into the cDC2 lineage
Although IRF8 plays a key role in cDC1 development, its role in committed cDC1 remains unclear. Here, Agace and colleagues demonstrate that IRF8 expression by committed cDC1 is required to maintain cDC1 identity but not survival and that its absence results in a conversion of cDC1 into cDC2-like cells. (Source: Immunity)
Source: Immunity - July 12, 2022 Category: Allergy & Immunology Authors: Telma Lan ça, Jonas Ungerbäck, Clément Da Silva, Thorsten Joeris, Fatemeh Ahmadi, Julien Vandamme, Marcus Svensson-Frej, Allan McI. Mowat, Knut Kotarsky, Mikael Sigvardsson, William W. Agace Tags: Article Source Type: research
Viral infection engenders bona fide and bystander subsets of lung-resident memory B cells through a permissive mechanism
Lung-resident memory B cells (MBCs) provide rapid protection against reinfection with airborne pathogens. Gregoire et al. demonstrate that two MBC subsets with discrete transcriptional programs reside in the lung peribronchial niche: “bona fide” virus-specific MBCs, which dominate recall responses, and “bystander” non-specific MBCs, which locally retain antigens as immune complexes. (Source: Immunity)
Source: Immunity - June 28, 2022 Category: Allergy & Immunology Authors: Claude Gregoire, Lionel Spinelli, Sergio Villazala-Merino, Laurine Gil, Mar ía Pía Holgado, Myriam Moussa, Chuang Dong, Ana Zarubica, Mathieu Fallet, Jean-Marc Navarro, Bernard Malissen, Pierre Milpied, Mauro Gaya Tags: Article Source Type: research
Very-low-density lipoprotein receptor-enhanced lipid metabolism in pancreatic stellate cells promotes pancreatic fibrosis
The role of lipoprotein disorder in chronic pancreatitis fibrotic microenvironment remains elusive. Yang et al. investigate that very-low-density lipoprotein receptor-enhanced lipid metabolism in pancreatic stellate cells promotes interleukin-33 expression and release, which is indispensable for the activation of pancreatic group 2 innate lymphoid cell and pancreatitis fibrosis progression. (Source: Immunity)
Source: Immunity - June 22, 2022 Category: Allergy & Immunology Authors: Xuguang Yang, Jie Chen, Jun Wang, Shuai Ma, Wenxue Feng, Zhihao Wu, Yangyang Guo, Hong Zhou, Wenli Mi, Wei Chen, Bo Yin, Yuli Lin Tags: Article Source Type: research
What SARS-CoV-2 does to our brains
Aschman et al. discuss possible mechanisms of neuroimmune interactions associated with SARS-CoV-2 infection. While there is currently no evidence of replicating virus in the CNS, sickness behavior as well as cognitive impairment after infections could be due to the effects of cytokines. Moreover, neuroimmunological diseases associated with COVID-19 may constitute post-infectious syndromes or are autoimmune-mediated processes triggered by acute viral infection. (Source: Immunity)
Source: Immunity - June 19, 2022 Category: Allergy & Immunology Authors: Tom Aschman, Ronja Mothes, Frank L. Heppner, Helena Radbruch Tags: Perspective Source Type: research
