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Yuriko Otake-Kasamoto, Hisako Kayama, Toshihiro Kishikawa, Shinichiro Shinzaki, Taku Tashiro, Takahiro Amano, Mizuki Tani, Takeo Yoshihara, Bo Li, Haruka Tani, Li Liu, Akio Hayashi, Daisuke Okuzaki, Daisuke Motooka, Shota Nakamura, Yukinori Okada, Hideki Iijima, Kiyoshi Takeda, Tetsuo Takehara
This study shows that Crohn’s disease–associated microbiota generate lysophosphatidylserines that promote Th1 responses by fueling glycolysis. Lysophosphatidylserine-induced aggravation of colitis is prevented by P2y10 deficiency in CD4+ T cells, demonstrating that dysbiotic microbiota-derived LysoPS exacerbates colitis by modulating Th1 cell metabolism.
Sara E. Schad, Andrew Chow, Levi Mangarin, Heng Pan, Jiajia Zhang, Nicholas Ceglia, Justina X. Caushi, Nicole Malandro, Roberta Zappasodi, Mathieu Gigoux, Daniel Hirschhorn, Sadna Budhu, Masataka Amisaki, Monica Arniella, David Redmond, Jamie Chaft, Patrick M. Forde, Justin F. Gainor, Matthew D. Hellmann, Vinod Balachandran, Sohrab Shah, Kellie N. Smith, Drew Pardoll, Olivier Elemento, Jedd D. Wolchok, Taha Merghoub
Antigen stimulation induces a subset of CD4+ and CD8+ T cells to differentiate into CD4+CD8+ T cell subsets gaining in polyfunctional characteristics within the tumor. Monitoring CD4+CD8+ T cells may thus favor the identification and selection of antigen-reactive T cells to drive clinical benefit.
Jad N. Kanbar, Shengyun Ma, Eleanor S. Kim, Nadia S. Kurd, Matthew S. Tsai, Tiffani Tysl, Christella E. Widjaja, Abigail E. Limary, Brian Yee, Zhaoren He, Yajing Hao, Xiang-Dong Fu, Gene W. Yeo, Wendy J. Huang, John T. Chang
Kanbar et al. show that the long noncoding RNA Malat1 impacts the differentiation of effector and memory CD8+ T cell subsets by virtue of preferential epigenetic repression of memory-associated genes in terminal effector cells through an interaction with Ezh2.
Nicholas Hanuscheck, Carine Thalman, Micaela Domingues, Samantha Schmaul, Muthuraman Muthuraman, Florian Hetsch, Manuela Ecker, Heiko Endle, Mohammadsaleh Oshaghi, Gianvito Martino, Tanja Kuhlmann, Katarzyna Bozek, Tim van Beers, Stefan Bittner, Jakob von Engelhardt, Johannes Vogt, Christina Francisca Vogelaar, Frauke Zipp
Neuroimmune interaction influences essential CNS processes. Hanuscheck et al. report on the expression of interleukin-4 receptor alpha at presynaptic terminals in mouse and the human brain. The modulation of neuronal IL-4R signaling alters the neuronal transcriptome, impacts synaptic transmission, and causes anxiety-related behavior.
Brief Definitive Report
Rie Hasebe, Kaoru Murakami, Masaya Harada, Nada Halaka, Hiroshi Nakagawa, Fuminori Kawano, Yoshinobu Ohira, Tadafumi Kawamoto, Fiona E. Yull, Timothy S. Blackwell, Junko Nio-Kobayashi, Toshihiko Iwanaga, Masahiko Watanabe, Nobuhiro Watanabe, Harumi Hotta, Toshihide Yamashita, Daisuke Kamimura, Yuki Tanaka, Masaaki Murakami
Local inflammation spreads to remote positions via sensory neuron–interneuron crosstalk using ATP. This neural pathway, or remote inflammation gateway reflex, may be a therapeutic target for inflammatory diseases with remote inflammation, such as rheumatoid arthritis.
Yikun Yao, Ping Du Jiang et al.
Yao et al. describe GIMAP6 deficiency in humans and mice showing immune dysfunction and susceptibility to bacterial infections. They find impaired autophagy in GIMAP6-deficient immune cells and define a functional complex composed of GIMAP6, GIMAP7, and GABARAPL2.
Jihye Han, Qingqing Wan, Goo-Young Seo, Kenneth Kim, Sarah el Baghdady, Jee H. Lee, Mitchell Kronenberg, Yun-Cai Liu
Hypoxia in club cells in the lung epithelium induces increased ILC2 responses, leading to enhanced inflammation and immunity. The mechanism, revealed by VHL deletion, is increased HIF2α driving the secretion of adrenomedullin, which activates ILC2.

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Current Issue
Volume 219,
Issue 5,
2 May 2022
Reviews & Opinions
Carl F. Ware, Michael Croft, Garry A. Neil
The cytokine LIGHT (TNFSF14) has emerged as an important modulator of innate and adaptive immune responses. Accumulating basic and clinical evidence points to the dysregulation of the LIGHT network as a disease-driving mechanism and supports the application of target-modifying therapeutics for disease intervention.
Mandy J. McGeachy
IL-17 promotes collagen deposition by cancer-associated fibroblasts and enhances immune exclusion of tumors.
Found in Translation
Véronique Dartois, Thomas Dick
Véronique Dartois and Thomas Dick discuss the evolution of drug discovery for the treatment of nontuberculous mycobacterial pulmonary disease (NTM-PD).

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