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Li Li, Eun-Seon Yoo, Xiujuan Li, Steven C. Wyler, Xiameng Chen, Rong Wan, Amanda G. Arnold, Shari G. Birnbaum, Lin Jia, Jong-Woo Sohn, Chen Liu
Li et al. develop a new mouse model that recapitulates risperidone-induced metabolic syndrome. Using a combination of transcriptomic, genetic, and electrophysiological approaches, they show that risperidone targets hypothalamic MC4Rs to cause weight gain and that setmelanotide, an MC4R agonist, mitigates its metabolic side effects.
Naveen Sharma, Oluwatomisin T. Atolagbe, Zhongqi Ge, James P. Allison
LILRB4 strongly suppresses tumor immunity, and LILRB4 blockade alleviates that suppression to provide antitumor efficacy. The authors show that LILRB4 is expressed largely on TAMs and suppresses antitumor immunity. Genetic deletion of LILRB4 or anti-LILRB4 antibody treatment modulates T cells to an effector phenotype and TAMs to a less immunosuppressive phenotype and increases survival against tumor challenge.
Trang T.T. Nguyen, Zhi-En Wang, Lin Shen, Andrew Schroeder, Walter Eckalbar, Arthur Weiss
T cell anergy is an important peripheral tolerance mechanism to prevent autoimmunity. Nguyen et al. find that T cell anergy develops in the periphery, not in the thymus, and depends upon Cbl-b but not Grail or PD-1.
Juliana M. Navia-Pelaez, Soo-Ho Choi, Luciano dos Santos Aggum Capettini, Yining Xia, Ayelet Gonen, Colin Agatisa-Boyle, Lauriane Delay, Gilson Gonçalves dos Santos, Glaucilene F. Catroli, Jungsu Kim, Jenny W. Lu, Benjamin Saylor, Holger Winkels, Christopher P. Durant, Yanal Ghosheh, Graham Beaton, Klaus Ley, Irina Kufareva, Maripat Corr, Tony L. Yaksh, Yury I. Miller
In a mouse model of chemotherapy-induced peripheral neuropathy, spinal microglia are characterized by the presence of inflammarafts—enlarged, cholesterol-enriched lipid rafts—which organize the inflammatory response. Manipulation of specific mechanisms regulating cholesterol metabolism normalizes inflammarafts and reprograms microglia, resulting in long-lasting alleviation of neuropathic pain.
Miwa Sasai, Ji Su Ma, Masaaki Okamoto, Kohei Nishino, Hikaru Nagaoka, Eizo Takashima, Ariel Pradipta, Youngae Lee, Hidetaka Kosako, Pann-Ghill Suh, Masahiro Yamamoto
Sasai, Ma, et al. demonstrate that PLCβ4 is specifically required for TCR signaling in CD8+ T cells but not CD4+ T cells, indicating that TCR signaling of CD8+ T cells is qualitatively distinct from that of CD4+ T cells.
Jung-Yeon Lim, Sascha H. Duttke, Turner S. Baker, Jihye Lee, Kristyne J. Gambino, Nicholas J. Venturini, Jessica Sook Yuin Ho, Simin Zheng, Yesai S. Fstkchyan, Vinodh Pillai, David C. Fajgenbaum, Ivan Marazzi, Christopher Benner, Minji Byun
Acquired mutations in DNMT3A are common in blood, but their impacts on mature immune cells are poorly understood. Lim et al. demonstrate that DNMT3A defects cause dichotomous DNA methylation defects at enhancers, leading to altered enhancer activity and abnormal gene expression in mature immune cells.
Rachel N. Cotton, Marcin Wegrecki, Tan-Yun Cheng, Yi-Ling Chen, Natacha Veerapen, Jérôme Le Nours, Dennis P. Orgill, Bohdan Pomahac, Simon G. Talbot, Richard Willis, John D. Altman, Annemieke de Jong, Ildiko Van Rhijn, Rachael A. Clark, Gurdyal S. Besra, Graham Ogg, Jamie Rossjohn, D. Branch Moody
CD1a is expressed on Langerhans cells, where it presents lipid antigens to activate T cells. However, skin cells also produce a natural lipid that binds CD1a and blocks T cell response as a mechanism to down-regulate autoreactivity.

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Current Issue
Volume 218,
Issue 5,
May 3, 2021
Reviews & Opinions
Vanessa Sancho-Shimizu, Petter Brodin, Aurélie Cobat, Catherine M. Biggs, Julie Toubiana, Carrie L. Lucas, Sarah E. Henrickson, Alexandre Belot, MIS-C@CHGE, Stuart G. Tangye, Joshua D. Milner, Michael Levin, Laurent Abel, Dusan Bogunovic, Jean-Laurent Casanova, Shen-Ying Zhang
SARS-CoV-2 is the trigger of MIS-C, which suggests that other viruses may trigger different forms of Kawasaki disease. The discovery of inborn errors of immunity underlying MIS-C would facilitate that of inborn errors of immunity to viruses underlying Kawasaki disease.
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Jacques Miller reflects on the identification of B cells and T cells.
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Ralf Küppers
Küppers outlines our understanding of the generation and function of B cells.

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