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Guillaume Harlé, Camille Kowalski, Juan Dubrot, Dale Brighouse, Gaëlle Clavel, Robert Pick, Natacha Bessis, Jennifer Niven, Christoph Scheiermann, Monique Gannagé, Stéphanie Hugues
The authors show that autophagy in lymphatic endothelial cells (LECs) dampens collagen-induced arthritis by regulating two distinct pathways: the promotion of T reg cells in LNs and the inhibition of S1P-dependent migration of pathogenic Th17 cells in inflamed organs.
Article
Tong Wu, Qinhui Liu, Yanping Li, Hong Li, Lei Chen, Xuping Yang, Qin Tang, Shiyun Pu, Jiangying Kuang, Rui Li, Ya Huang, Jinhang Zhang, Zijing Zhang, Jian Zhou, Cuiyuan Huang, Guorong Zhang, Yingnan Zhao, Min Zou, Wei Jiang, Li Mo, Jinhan He
This article shows Manf, a feeding-induced hepatokine, can directly promote browning of white adipose tissue via the p38 MAPK pathway and consequently protect mice against high-fat diet–induced obesity.
Article
James S. Chavez, Jennifer L. Rabe, Dirk Loeffler, Kelly C. Higa, Giovanny Hernandez, Taylor S. Mills, Nouraiz Ahmed, Rachel L. Gessner, Zhonghe Ke, Beau M. Idler, Katia E. Niño, Hyunmin Kim, Jason R. Myers, Brett M. Stevens, Pavel Davizon-Castillo, Craig T. Jordan, Hideaki Nakajima, John Ashton, Robert S. Welner, Timm Schroeder, James DeGregori, Eric M. Pietras
In this article, Chavez et al. show that the myeloid transcription factor PU.1 plays an essential role in maintaining hematopoietic stem cell (HSC) quiescence and homeostatic protein synthesis rates, thereby regulating HSC pool size and cell cycle activity during chronic inflammatory stress.
Article
Zhong-Yin Li, Rosemary E. Morman, Emma Hegermiller, Mengxi Sun, Elizabeth T. Bartom, Mark Maienschein-Cline, Mikael Sigvardsson, Barbara L. Kee
ID2 is an essential transcription factor for natural killer cell development. Through epistasis analysis, Li et al. show that ID2 controls the amplitude of TCF1 and allows for its temporal downregulation, thereby supporting natural killer cell maturation.
Brief Definitive Report
Lara Wahlster, Jeffrey M. Verboon, Leif S. Ludwig, Susan C. Black, Wendy Luo, Kopal Garg, Richard A. Voit, Ryan L. Collins, Kiran Garimella, Maura Costello, Katherine R. Chao, Julia K. Goodrich, Stephanie P. DiTroia, Anne O’Donnell-Luria, Michael E. Talkowski, Alan D. Michelson, Alan B. Cantor, Vijay G. Sankaran
Wahlster, Verboon, et al. identify and functionally characterize a complex structural variant in a family with thrombocytopenia that results in a WAC-ANKRD26 fusion transcript encoding a shortened form of ANKRD26, whose expression during hematopoiesis is deregulated, thereby resulting in disease.
Brief Definitive Report
Chun I. Yu, Jan Martinek, Te-Chia Wu, Kyung In Kim, Joshy George, Elaheh Ahmadzadeh, Rick Maser, Florentina Marches, Patrick Metang, Pierre Authie, Vanessa K.P. Oliveira, Victor G. Wang, Jeffrey H. Chuang, Paul Robson, Jacques Banchereau, Karolina Palucka
Colonization of visceral organs with melanoma in humanized NSG-SGM3 mice is dependent upon human CD33+CD11b+CD117+ progenitor cells. A gene signature of KIT/CD117–expressing CD33+ subset correlates with decreased overall survival in TCGA melanoma samples and represents a novel candidate biomarker.
Article
Joseph E. Rupert, Ashok Narasimhan, Daenique H.A. Jengelley, Yanlin Jiang, Jianguo Liu, Ernie Au, Libbie M. Silverman, George Sandusky, Andrea Bonetto, Sha Cao, Xiaoyu Lu, Thomas M. O’Connell, Yunlong Liu, Leonidas G. Koniaris, Teresa A. Zimmers
Cachexia increases morbidity and mortality. Rupert et al. show PDAC cachexia results from tissue crosstalk via an IL-6 trans-signaling loop. Malignant cells signal via IL-6 to muscle and fat, muscle to fat via sIL6R, and fat to muscle via lipids and IL-6.

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Current Issue
Volume 218,
Issue 4,
April 5, 2021
Reviews & Opinions
Insights
Ross M. Kedl
Virus-specific immune responses persist over time in subjects recovering from asymptomatic SARS-CoV-2 infection.
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Paola de Candia, Francesco Prattichizzo, Silvia Garavelli, Carlo Alviggi, Antonio La Cava, Giuseppe Matarese
This review summarizes the pleiotropic functions of leptin, whose capability to regulate both energy homeostasis and inflammation has unveiled the biological determinants of human obesity and the interconnection among dysmetabolic conditions, the onset of autoimmune diseases, and cancer in more affluent countries.
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Loss-of-function mutations in DNaseL13, the enzyme that restricts the amount of microparticle-associated DNA, cause SLE in humans and mice. In this issue of JEM, Hartl et al. uncover a reduction in plasma DNASE1L3 enzymatic activity due to the presence of autoantibodies in patients with non-familial SLE.

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