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Matthew DeBerge, Connor Lantz, Shirley Dehn, David P. Sullivan, Anja M. van der Laan, Hans W.M. Niessen, Margaret E. Flanagan, Daniel J. Brat, Matthew J. Feinstein, Sunjay Kaushal, Lisa D. Wilsbacher, Edward B. Thorp
Following myocardial infarction, tissue ischemia leads to activation of hypoxia-inducible factors. DeBerge et al. demonstrate that HIF-1α and HIF-2α activation in myeloid cells antagonizes cardiac repair pathways through cleavage of cardioprotective MerTK and suppression of anti-inflammatory mitochondrial metabolism, respectively.
Keitaro Fukuda, Ken Okamura, Rebecca L. Riding, Xueli Fan, Khashayar Afshari, Nazgol-Sadat Haddadi, Sean M. McCauley, Mehmet H. Guney, Jeremy Luban, Takeru Funakoshi, Tomonori Yaguchi, Yutaka Kawakami, Anastasia Khvorova, Katherine A. Fitzgerald, John E. Harris
Fukuda et al. demonstrate that AIM2 expression in DCs within human melanoma is a poor prognostic sign and that AIM2-deficient DC vaccination enhances melanoma immunotherapeutic responses by promoting STING-induced IFN secretion as well as limiting IL-1β and IL-18 production.
John Podstawka, Sarthak Sinha, Carlos H. Hiroki, Nicole Sarden, Elise Granton, Elodie Labit, Jung Hwan Kim, Graciela Andonegui, Yuefei Lou, Brendan D. Snarr, Donald C. Sheppard, Nicole L. Rosin, Jeff Biernaskie, Bryan G. Yipp
Genetically diverse IgM+ peripheral B cells reside in the lung microvasculature and dampen neutrophil-mediated lung inflammation via lipoxins. Podstawka et al. reveal that transitional B cells marginate in the lung capillaries, where they dampen neutrophil inflammation. These discoveries help elucidate regulatory mechanisms that attenuate acute lung inflammation, which, when unchecked, can lead to acute respiratory distress syndrome and pulmonary failure.
Courtney Mowat, Shayla R. Mosley, Afshin Namdar, Daniel Schiller, Kristi Baker
Mowat et al. show that anti-tumor immunity in dMMR CRCs relies on recruitment and retention of systemic CD8+ T cells. This is driven by extensive genomic instability that upregulates CCL5 and CXCL10 in the CRC cells by endogenously activating cGAS/STING and type I IFN signaling.
Anna-Maria Herzner, Zia Khan, Eric L. Van Nostrand, Sara Chan, Trinna Cuellar, Ronald Chen, Ximo Pechuan-Jorge, Laszlo Komuves, Margaret Solon, Zora Modrusan, Benjamin Haley, Gene W. Yeo, Timothy W. Behrens, Matthew L. Albert
hnRNPC prevents release of inverted-repeat Alu double-stranded RNA into the cytosol by masking cryptic splice sites. Herzner et al. found that deficiency in hnRNPC led to dysregulation of splicing and increased abundance of intronic double-stranded RNA, which together with ADAR deficiency resulted in a synergistic increase in spontaneous MDA5-dependent IFN responses.
Technical Advances and Resources
Davide Pisu, Lu Huang, Vipin Narang, Monique Theriault, Gabrielle Lê-Bury, Bernett Lee, Agnes E. Lakudzala, David T. Mzinza, David V. Mhango, Steven C. Mitini-Nkhoma, Kondwani C. Jambo, Amit Singhal, Henry C. Mwandumba, David G. Russell
Through scRNA-seq and ATAC-seq, Pisu et al. characterize specific lung macrophage subsets that either restrict or promote M. tuberculosis growth. Comparable macrophage populations are present in the human airways, and cells show evidence of epigenetic imprinting.
Cecilia B. Cavazzoni, Vicente B.T. Bozza, Tostes C.V. Lucas, Luciana Conde, Bruno Maia, Luka Mesin, Ariën Schiepers, Jonatan Ersching, Romulo L.S. Neris, Jonas N. Conde, Diego R. Coelho, Tulio M. Lima, Renata G.F. Alvim, Leda R. Castilho, Heitor A. de Paula Neto, Ronaldo Mohana-Borges, Iranaia Assunção-Miranda, Alberto Nobrega, Gabriel D. Victora, Andre M. Vale
Using an immunocompetent mouse model of ZIKV infection, Cavazzoni et al. describe an immunodominant anti-NS1 humoral response characterized by autoreactive germinal center B cells, both cross-reactive and non-cross-reactive with NS1, exhibiting a paucity of somatic hypermutations, suggesting a broad breakage of self-tolerance in this viral infection model.

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Volume 218,
Issue 7,
July 5, 2021
Reviews & Opinions
Davide F. Robbiani, Daniel Růžek
The NS1 protein of flaviviruses is taking center stage. Recent work has made it an attractive target for development of vaccines and immunotherapeutics. Cavazzoni and colleagues now reveal a dark side to NS1, linking it to the development of self-reactive antibodies.
Matae Ahn, Lin-Fa Wang
Ahn and Wang discuss the translational potential of the bat model for treating human diseases.
Andrew W. Daman, Steven Z. Josefowicz
Here, we will summarize the historical and current understanding of the stepwise assembly and function of factors that regulate ifnb gene transcription.

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