Pub Date : 2024-11-21DOI: 10.1016/j.immuni.2024.10.015
Siyu Sun, Eunae You, Jungeui Hong, David Hoyos, Isabella S. Del Priore, Kaloyan M. Tsanov, Om Mattagajasingh, Andrea Di Gioacchino, Sajid A. Marhon, Jonathan Chacon-Barahona, Hao Li, Hua Jiang, Samira Hozeifi, Omar Rosas-Bringas, Katherine H. Xu, Yuhui Song, Evan R. Lang, Alexandra S. Rojas, Linda T. Nieman, Bidish K. Patel, Benjamin D. Greenbaum
To thrive, cancer cells must navigate acute inflammatory signaling accompanying oncogenic transformation, such as via overexpression of repeat elements. We examined the relationship between immunostimulatory repeat expression, tumor evolution, and the tumor-immune microenvironment. Integration of multimodal data from a cohort of pancreatic ductal adenocarcinoma (PDAC) patients revealed expression of specific Alu repeats predicted to form double-stranded RNAs (dsRNAs) and trigger retinoic-acid-inducible gene I (RIG-I)-like-receptor (RLR)-associated type-I interferon (IFN) signaling. Such Alu-derived dsRNAs also anti-correlated with pro-tumorigenic macrophage infiltration in late stage tumors. We defined two complementary pathways whereby PDAC may adapt to such anti-tumorigenic signaling. In mutant TP53 tumors, ORF1p from long interspersed nuclear element (LINE)-1 preferentially binds Alus and decreases their expression, whereas adenosine deaminases acting on RNA 1 (ADAR1) editing primarily reduces dsRNA formation in wild-type TP53 tumors. Depletion of either LINE-1 ORF1p or ADAR1 reduced tumor growth in vitro. The fact that tumors utilize multiple pathways to mitigate immunostimulatory repeats implies the stress from their expression is a fundamental phenomenon to which PDAC, and likely other tumors, adapt.
{"title":"Cancer cells restrict immunogenicity of retrotransposon expression via distinct mechanisms","authors":"Siyu Sun, Eunae You, Jungeui Hong, David Hoyos, Isabella S. Del Priore, Kaloyan M. Tsanov, Om Mattagajasingh, Andrea Di Gioacchino, Sajid A. Marhon, Jonathan Chacon-Barahona, Hao Li, Hua Jiang, Samira Hozeifi, Omar Rosas-Bringas, Katherine H. Xu, Yuhui Song, Evan R. Lang, Alexandra S. Rojas, Linda T. Nieman, Bidish K. Patel, Benjamin D. Greenbaum","doi":"10.1016/j.immuni.2024.10.015","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.10.015","url":null,"abstract":"To thrive, cancer cells must navigate acute inflammatory signaling accompanying oncogenic transformation, such as via overexpression of repeat elements. We examined the relationship between immunostimulatory repeat expression, tumor evolution, and the tumor-immune microenvironment. Integration of multimodal data from a cohort of pancreatic ductal adenocarcinoma (PDAC) patients revealed expression of specific Alu repeats predicted to form double-stranded RNAs (dsRNAs) and trigger retinoic-acid-inducible gene I (RIG-I)-like-receptor (RLR)-associated type-I interferon (IFN) signaling. Such Alu-derived dsRNAs also anti-correlated with pro-tumorigenic macrophage infiltration in late stage tumors. We defined two complementary pathways whereby PDAC may adapt to such anti-tumorigenic signaling. In mutant <em>TP53</em> tumors, ORF1p from long interspersed nuclear element (LINE)-1 preferentially binds Alus and decreases their expression, whereas adenosine deaminases acting on RNA 1 (ADAR1) editing primarily reduces dsRNA formation in wild-type <em>TP53</em> tumors. Depletion of either LINE-1 ORF1p or ADAR1 reduced tumor growth <em>in vitro</em>. The fact that tumors utilize multiple pathways to mitigate immunostimulatory repeats implies the stress from their expression is a fundamental phenomenon to which PDAC, and likely other tumors, adapt.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"192 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142678284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-20DOI: 10.1016/j.immuni.2024.10.010
Yutao Wang, Yanbo Zhang, Kyungsub Kim, Jichang Han, Daniel Okin, Zhaozhao Jiang, Liang Yang, Arum Subramaniam, Terry K. Means, Frank O. Nestlé, Katherine A. Fitzgerald, Gwendalyn J. Randolph, Cammie F. Lesser, Jonathan C. Kagan, Diane Mathis, Christophe Benoist
Ligand-dependent transcription factors of the nuclear receptor (NR) family regulate diverse aspects of metazoan biology, enabling communications between distant organs via small lipophilic molecules. Here, we examined the impact of each of 35 NRs on differentiation and homeostatic maintenance of all major immunological cell types in vivo through a “Rainbow-CRISPR” screen. Receptors for retinoic acid exerted the most frequent cell-specific roles. NR requirements varied for resident macrophages of different tissues. Deletion of either Rxra or Rarg reduced frequencies of GATA6+ large peritoneal macrophages (LPMs). Retinoid X receptor alpha (RXRα) functioned conventionally by orchestrating LPM differentiation through chromatin and transcriptional regulation, whereas retinoic acid receptor gamma (RARγ) controlled LPM survival by regulating pyroptosis via association with the inflammasome adaptor ASC. RARγ antagonists activated caspases, and RARγ agonists inhibited cell death induced by several inflammasome activators. Our findings provide a broad view of NR function in the immune system and reveal a noncanonical role for a retinoid receptor in modulating inflammasome pathways.
核受体（NR）家族的配体依赖性转录因子调控着类人猿生物学的各个方面，通过亲脂性小分子实现远距离器官之间的通讯。在这里，我们通过 "彩虹-CRISPR "筛选研究了 35 种 NR 对体内所有主要免疫细胞类型的分化和平衡维持的影响。视黄酸受体发挥了最常见的细胞特异性作用。不同组织的常驻巨噬细胞对 NR 的需求各不相同。Rxra或Rarg的缺失会降低GATA6+大腹腔巨噬细胞（LPMs）的频率。视黄酸 X 受体α（RXRα）的传统功能是通过染色质和转录调控来协调 LPM 的分化，而视黄酸受体γ（RARγ）则通过与炎性体适配体 ASC 的结合来调控热凋亡，从而控制 LPM 的存活。RARγ拮抗剂可激活caspases，而RARγ激动剂可抑制几种炎症小体激活剂诱导的细胞死亡。我们的发现为 NR 在免疫系统中的功能提供了一个广阔的视角，并揭示了视黄醇受体在调节炎性体通路中的非经典作用。
{"title":"A pan-family screen of nuclear receptors in immunocytes reveals ligand-dependent inflammasome control","authors":"Yutao Wang, Yanbo Zhang, Kyungsub Kim, Jichang Han, Daniel Okin, Zhaozhao Jiang, Liang Yang, Arum Subramaniam, Terry K. Means, Frank O. Nestlé, Katherine A. Fitzgerald, Gwendalyn J. Randolph, Cammie F. Lesser, Jonathan C. Kagan, Diane Mathis, Christophe Benoist","doi":"10.1016/j.immuni.2024.10.010","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.10.010","url":null,"abstract":"Ligand-dependent transcription factors of the nuclear receptor (NR) family regulate diverse aspects of metazoan biology, enabling communications between distant organs via small lipophilic molecules. Here, we examined the impact of each of 35 NRs on differentiation and homeostatic maintenance of all major immunological cell types <em>in vivo</em> through a “Rainbow-CRISPR” screen. Receptors for retinoic acid exerted the most frequent cell-specific roles. NR requirements varied for resident macrophages of different tissues. Deletion of either <em>Rxra</em> or <em>Rarg</em> reduced frequencies of GATA6<sup>+</sup> large peritoneal macrophages (LPMs). Retinoid X receptor alpha (RXRα) functioned conventionally by orchestrating LPM differentiation through chromatin and transcriptional regulation, whereas retinoic acid receptor gamma (RARγ) controlled LPM survival by regulating pyroptosis via association with the inflammasome adaptor ASC. RARγ antagonists activated caspases, and RARγ agonists inhibited cell death induced by several inflammasome activators. Our findings provide a broad view of NR function in the immune system and reveal a noncanonical role for a retinoid receptor in modulating inflammasome pathways.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"53 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-20DOI: 10.1016/j.immuni.2024.10.012
Benedikt S. Saller, Svenja Wöhrle, Larissa Fischer, Clara Dufossez, Isabella L. Ingerl, Susanne Kessler, Maria Mateo-Tortola, Oliver Gorka, Felix Lange, Yurong Cheng, Emilia Neuwirt, Adinarayana Marada, Christoph Koentges, Chiara Urban, Philipp Aktories, Peter Reuther, Sebastian Giese, Susanne Kirschnek, Carolin Mayer, Johannes Pilic, Olaf Groß
How mitochondria reconcile roles in functionally divergent cell death pathways of apoptosis and NLRP3 inflammasome-mediated pyroptosis remains elusive, as is their precise role in NLRP3 activation and the evolutionarily conserved physiological function of NLRP3. Here, we have shown that when cells were challenged simultaneously, apoptosis was inhibited and NLRP3 activation prevailed. Apoptosis inhibition by structurally diverse NLRP3 activators, including nigericin, imiquimod, extracellular ATP, particles, and viruses, was not a consequence of inflammasome activation but rather of their effects on mitochondria. NLRP3 activators turned out as oxidative phosphorylation (OXPHOS) inhibitors, which we found to disrupt mitochondrial cristae architecture, leading to trapping of cytochrome c. Although this effect was alone not sufficient for NLRP3 activation, OXPHOS inhibitors became triggers of NLRP3 when combined with resiquimod or Yoda-1, suggesting that NLRP3 activation requires two simultaneous cellular signals, one of mitochondrial origin. Therefore, OXPHOS and apoptosis inhibition by NLRP3 activators provide stringency in cell death decisions.
{"title":"Acute suppression of mitochondrial ATP production prevents apoptosis and provides an essential signal for NLRP3 inflammasome activation","authors":"Benedikt S. Saller, Svenja Wöhrle, Larissa Fischer, Clara Dufossez, Isabella L. Ingerl, Susanne Kessler, Maria Mateo-Tortola, Oliver Gorka, Felix Lange, Yurong Cheng, Emilia Neuwirt, Adinarayana Marada, Christoph Koentges, Chiara Urban, Philipp Aktories, Peter Reuther, Sebastian Giese, Susanne Kirschnek, Carolin Mayer, Johannes Pilic, Olaf Groß","doi":"10.1016/j.immuni.2024.10.012","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.10.012","url":null,"abstract":"How mitochondria reconcile roles in functionally divergent cell death pathways of apoptosis and NLRP3 inflammasome-mediated pyroptosis remains elusive, as is their precise role in NLRP3 activation and the evolutionarily conserved physiological function of NLRP3. Here, we have shown that when cells were challenged simultaneously, apoptosis was inhibited and NLRP3 activation prevailed. Apoptosis inhibition by structurally diverse NLRP3 activators, including nigericin, imiquimod, extracellular ATP, particles, and viruses, was not a consequence of inflammasome activation but rather of their effects on mitochondria. NLRP3 activators turned out as oxidative phosphorylation (OXPHOS) inhibitors, which we found to disrupt mitochondrial cristae architecture, leading to trapping of cytochrome <em>c</em>. Although this effect was alone not sufficient for NLRP3 activation, OXPHOS inhibitors became triggers of NLRP3 when combined with resiquimod or Yoda-1, suggesting that NLRP3 activation requires two simultaneous cellular signals, one of mitochondrial origin. Therefore, OXPHOS and apoptosis inhibition by NLRP3 activators provide stringency in cell death decisions.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"178 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142673214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-18DOI: 10.1016/j.immuni.2024.10.013
Hsiao-Wei Tsao, Seth Anderson, Kenneth J. Finn, Jonathan J. Perera, Lomax F. Pass, Emily M. Schneider, Aiping Jiang, Rachel Fetterman, Cun Lan Chuong, Kaiya Kozuma, Marcia M. Stickler, Marc Creixell, Susan Klaeger, Kshiti Meera Phulphagar, Suzanna Rachimi, Eva K. Verzani, Niclas Olsson, Juan Dubrot, Matthew F. Pech, Whitney Silkworth, Robert T. Manguso
The aminopeptidase, endoplasmic reticulum aminopeptidase 1 (ERAP1), trims peptides for loading into major histocompatibility complex class I (MHC class I), and loss of this activity has broad effects on the MHC class I peptidome. Here, we investigated the impact of targeting ERAP1 in immune checkpoint blockade (ICB), as MHC class I interactions mediate both activating and inhibitory functions in antitumor immunity. Loss of ERAP sensitized mouse tumor models to ICB, and this sensitivity depended on CD8+ T cells and natural killer (NK) cells. In vivo suppression screens revealed that Erap1 deletion inactivated the inhibitory NKG2A-HLA-E checkpoint, which requires presentation of a restricted set of invariant epitopes (VL9) on HLA-E. Loss of ERAP altered the HLA-E peptidome, preventing NKG2A engagement. In humans, ERAP1 and ERAP2 showed functional redundancy for the processing and presentation of VL9, and loss of both inactivated the NKG2A checkpoint in cancer cells. Thus, loss of ERAP phenocopies the inhibition of the NKG2A-HLA-E pathway and represents an attractive approach to inhibit this critical checkpoint.
氨肽酶--内质网氨肽酶 1（ERAP1）--修饰肽段以装入主要组织相容性复合体 I 类（MHC I 类），而这种活性的丧失会对 MHC I 类肽组产生广泛的影响。在这里，我们研究了靶向ERAP1对免疫检查点阻断（ICB）的影响，因为MHC I类相互作用在抗肿瘤免疫中同时介导激活和抑制功能。缺失ERAP会使小鼠肿瘤模型对ICB敏感，而这种敏感性取决于CD8+ T细胞和自然杀伤（NK）细胞。体内抑制筛选显示，Erap1缺失会使抑制性NKG2A-HLA-E检查点失活，而抑制性NKG2A-HLA-E检查点需要HLA-E上一组受限的不变表位（VL9）。ERAP的缺失改变了HLA-E肽组，阻止了NKG2A的参与。在人类中，ERAP1和ERAP2在处理和呈现VL9方面表现出功能冗余，两者的缺失会使癌细胞中的NKG2A检查点失活。因此，ERAP的缺失表征了对NKG2A-HLA-E通路的抑制，是抑制这一关键检查点的一种有吸引力的方法。
{"title":"Targeting the aminopeptidase ERAP enhances antitumor immunity by disrupting the NKG2A-HLA-E inhibitory checkpoint","authors":"Hsiao-Wei Tsao, Seth Anderson, Kenneth J. Finn, Jonathan J. Perera, Lomax F. Pass, Emily M. Schneider, Aiping Jiang, Rachel Fetterman, Cun Lan Chuong, Kaiya Kozuma, Marcia M. Stickler, Marc Creixell, Susan Klaeger, Kshiti Meera Phulphagar, Suzanna Rachimi, Eva K. Verzani, Niclas Olsson, Juan Dubrot, Matthew F. Pech, Whitney Silkworth, Robert T. Manguso","doi":"10.1016/j.immuni.2024.10.013","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.10.013","url":null,"abstract":"The aminopeptidase, endoplasmic reticulum aminopeptidase 1 (ERAP1), trims peptides for loading into major histocompatibility complex class I (MHC class I), and loss of this activity has broad effects on the MHC class I peptidome. Here, we investigated the impact of targeting ERAP1 in immune checkpoint blockade (ICB), as MHC class I interactions mediate both activating and inhibitory functions in antitumor immunity. Loss of ERAP sensitized mouse tumor models to ICB, and this sensitivity depended on CD8<sup>+</sup> T cells and natural killer (NK) cells. <em>In vivo</em> suppression screens revealed that <em>Erap1</em> deletion inactivated the inhibitory NKG2A-HLA-E checkpoint, which requires presentation of a restricted set of invariant epitopes (VL9) on HLA-E. Loss of ERAP altered the HLA-E peptidome, preventing NKG2A engagement. In humans, ERAP1 and ERAP2 showed functional redundancy for the processing and presentation of VL9, and loss of both inactivated the NKG2A checkpoint in cancer cells. Thus, loss of ERAP phenocopies the inhibition of the NKG2A-HLA-E pathway and represents an attractive approach to inhibit this critical checkpoint.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"99 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142665526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-15DOI: 10.1016/j.immuni.2024.10.011
Georg Schett, Carl H. June
Several recent reports have demonstrated that B cell-targeting chimeric antigen receptor (CAR) T cells offer a viable treatment option for patients with autoantibody-mediated autoimmune diseases. To present additional data on this therapy and discuss strategies for more efficient clinical translation, leading experts in CAR T cell therapy for autoimmunity from various countries, including China, Germany, and the United States, convened at the “1st International Autoimmune CAR T Innovators Summit” in Grassau, Germany, from May 10–12, 2024. The summit showcased additional insights of CAR T cell therapy in diverse autoimmune diseases and provided platforms for discussions on key questions through workshops and roundtables. Here, we summarize the recent findings and key developments reported at the summit.
{"title":"CAR T cells in autoimmune disease: On the road to remission","authors":"Georg Schett, Carl H. June","doi":"10.1016/j.immuni.2024.10.011","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.10.011","url":null,"abstract":"Several recent reports have demonstrated that B cell-targeting chimeric antigen receptor (CAR) T cells offer a viable treatment option for patients with autoantibody-mediated autoimmune diseases. To present additional data on this therapy and discuss strategies for more efficient clinical translation, leading experts in CAR T cell therapy for autoimmunity from various countries, including China, Germany, and the United States, convened at the “1st International Autoimmune CAR T Innovators Summit” in Grassau, Germany, from May 10–12, 2024. The summit showcased additional insights of CAR T cell therapy in diverse autoimmune diseases and provided platforms for discussions on key questions through workshops and roundtables. Here, we summarize the recent findings and key developments reported at the summit.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"9 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-13DOI: 10.1016/j.immuni.2024.10.002
Saborni Chakraborty, Bowie Yik-Ling Cheng, Desmond L. Edwards, Joseph C. Gonzalez, David Kung-Chun Chiu, Hong Zheng, Courtney Scallan, Xinrong Guo, Gene S. Tan, Greg P. Coffey, Pamela B. Conley, Patrick S. Hume, William J. Janssen, Derek E. Byers, Philip A. Mudd, Jeffery Taubenberger, Matthew Memoli, Mark M. Davis, Katrin F. Chua, Michael S. Diamond, Taia T. Wang
While most respiratory viral infections resolve with little harm to the host, severe symptoms arise when infection triggers an aberrant inflammatory response that damages lung tissue. Host regulators of virally induced lung inflammation have not been well defined. Here, we show that enrichment for sialylated, but not asialylated immunoglobulin G (IgG), predicted mild influenza disease in humans and was broadly protective against heterologous influenza viruses in a murine challenge model. Mechanistic studies show that sialylated IgG mediated this protection by inducing the transcription factor repressor element-1 silencing transcription factor (REST), which repressed nuclear factor κB (NF-κB)-driven responses, preventing severe lung inflammation and protecting lung function during influenza infection. Therapeutic administration of a recombinant, sialylated Fc molecule in clinical development similarly activated REST and protected against severe influenza disease, demonstrating that this pathway could be clinically harnessed. Overall, induction of REST through sialylated IgG signaling is a strategy to limit inflammatory disease sequelae in infections caused by antigenically distinct influenza strains.
{"title":"Sialylated IgG induces the transcription factor REST in alveolar macrophages to protect against lung inflammation and severe influenza disease","authors":"Saborni Chakraborty, Bowie Yik-Ling Cheng, Desmond L. Edwards, Joseph C. Gonzalez, David Kung-Chun Chiu, Hong Zheng, Courtney Scallan, Xinrong Guo, Gene S. Tan, Greg P. Coffey, Pamela B. Conley, Patrick S. Hume, William J. Janssen, Derek E. Byers, Philip A. Mudd, Jeffery Taubenberger, Matthew Memoli, Mark M. Davis, Katrin F. Chua, Michael S. Diamond, Taia T. Wang","doi":"10.1016/j.immuni.2024.10.002","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.10.002","url":null,"abstract":"While most respiratory viral infections resolve with little harm to the host, severe symptoms arise when infection triggers an aberrant inflammatory response that damages lung tissue. Host regulators of virally induced lung inflammation have not been well defined. Here, we show that enrichment for sialylated, but not asialylated immunoglobulin G (IgG), predicted mild influenza disease in humans and was broadly protective against heterologous influenza viruses in a murine challenge model. Mechanistic studies show that sialylated IgG mediated this protection by inducing the transcription factor repressor element-1 silencing transcription factor (REST), which repressed nuclear factor κB (NF-κB)-driven responses, preventing severe lung inflammation and protecting lung function during influenza infection. Therapeutic administration of a recombinant, sialylated Fc molecule in clinical development similarly activated REST and protected against severe influenza disease, demonstrating that this pathway could be clinically harnessed. Overall, induction of REST through sialylated IgG signaling is a strategy to limit inflammatory disease sequelae in infections caused by antigenically distinct influenza strains.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"3 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142601061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-12DOI: 10.1016/j.immuni.2024.10.005
Andrea Dorfleutner, Christian Stehlik, Caroline A. Jefferies
The role of type I interferon (IFN-I) in systemic lupus erythematosus (SLE) is well documented, but the role of interleukin (IL)-1β remains elusive. In this issue of Immunity, Caielli et al. identified an SLE monocyte population coproducing IL-1β and IFN-I and described how mitochondrial nucleic-acid-containing RBCs engage cGAS/STING, RIG-I, MDA5, and NLRP3 for unconventional IL-1β release.
{"title":"Mx1-ing it up—Mitochondrial relay for interferon-dependent, unconventional IL-1β release in SLE monocytes","authors":"Andrea Dorfleutner, Christian Stehlik, Caroline A. Jefferies","doi":"10.1016/j.immuni.2024.10.005","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.10.005","url":null,"abstract":"The role of type I interferon (IFN-I) in systemic lupus erythematosus (SLE) is well documented, but the role of interleukin (IL)-1β remains elusive. In this issue of <em>Immunity</em>, Caielli et al. identified an SLE monocyte population coproducing IL-1β and IFN-I and described how mitochondrial nucleic-acid-containing RBCs engage cGAS/STING, RIG-I, MDA5, and NLRP3 for unconventional IL-1β release.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"4 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-12DOI: 10.1016/j.immuni.2024.10.008
Kalle Liimatta, Elina I. Zúñiga
Tissue-resident memory T (TRM) cells adapt to diverse environments, providing local long-term protection. In this issue of Immunity, Obers et al. and Raynor et al. demonstrate how diet, commensals, and host factors determine TRM cell development, maintenance, and function across tissues.
组织驻留记忆 T 细胞（TRM）能适应不同的环境，提供局部长期保护。在本期《免疫》杂志上，Obers 等人和 Raynor 等人展示了饮食、共生动物和宿主因素如何决定 TRM 细胞在不同组织中的发育、维持和功能。
{"title":"Home at last: Mixed signals guide memory T cells to residency","authors":"Kalle Liimatta, Elina I. Zúñiga","doi":"10.1016/j.immuni.2024.10.008","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.10.008","url":null,"abstract":"Tissue-resident memory T (T<sub>RM</sub>) cells adapt to diverse environments, providing local long-term protection. In this issue of <em>Immunity</em>, Obers et al. and Raynor et al. demonstrate how diet, commensals, and host factors determine T<sub>RM</sub> cell development, maintenance, and function across tissues.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"80 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-12DOI: 10.1016/j.immuni.2024.10.009
Elena Donders, Diether Lambrechts
Resistance to tyrosine kinase inhibitors (TKIs) in lung cancer brain metastasis (LCBM) remains a clinical challenge. Recently in Cancer Cell, Fu et al. reveal how TKIs reshape the immune microenvironment of LCBM and propose CTLA4 blockade as a promising strategy to overcome resistance.
{"title":"TKI resistance in brain metastasis: A CTLA4 state of mind","authors":"Elena Donders, Diether Lambrechts","doi":"10.1016/j.immuni.2024.10.009","DOIUrl":"https://doi.org/10.1016/j.immuni.2024.10.009","url":null,"abstract":"Resistance to tyrosine kinase inhibitors (TKIs) in lung cancer brain metastasis (LCBM) remains a clinical challenge. Recently in <em>Cancer Cell</em>, Fu et al. reveal how TKIs reshape the immune microenvironment of LCBM and propose CTLA4 blockade as a promising strategy to overcome resistance.","PeriodicalId":13269,"journal":{"name":"Immunity","volume":"95 1","pages":""},"PeriodicalIF":32.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-12DOI: 10.1016/j.immuni.2024.10.006
Jan Remsik, Adrienne Boire
Insufficient influx of T cells into the tumor microenvironment, including brain metastasis, dramatically limits efficacy of conventional immunotherapy. In this issue of Immunity, Messmer et al. interrogate spatiotemporal dependencies of melanoma brain metastasis T cell infiltration by intravital microscopy. They find that T cells enter these brain tumors through peritumoral venous vessels and can be stimulated with immunotherapy.
T细胞涌入肿瘤微环境（包括脑转移瘤）不足，极大地限制了传统免疫疗法的疗效。在本期《免疫》杂志上，Messmer 等人通过体内显微镜研究了黑色素瘤脑转移瘤 T 细胞浸润的时空依赖性。他们发现，T细胞通过瘤周静脉血管进入这些脑瘤，并能通过免疫疗法得到刺激。
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