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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.
Shu Hisata, Alexandra C. Racanelli, Pouneh Kermani, Ryan Schreiner, Sean Houghton, Brisa Palikuqi, Balvir Kunar, Aiyuan Zhou, Keith McConn, Allyson Capili, David Redmond, Daniel J. Nolan, Michael Ginsberg, Bi-Sen Ding, Fernando J. Martinez, Joseph M. Scandura, Suzanne M. Cloonan, Shahin Rafii, Augustine M.K. Choi
We tested the role of endothelial dysfunction in the development of COPD/emphysema. We found that restoration of lung endothelial cells and blockade of endothelial-derived leucine-rich α-2-glycoprotein perturbs the pathogenesis of COPD/emphysema.
Zuojia Chen, Jialie Luo, Jian Li, Girak Kim, Eric S. Chen, Sheng Xiao, Scott B. Snapper, Bin Bao, Dingding An, Richard S. Blumberg, Cheng-hui Lin, Sui Wang, Jiaxin Zhong, Kuai Liu, Qiyuan Li, Chuan Wu, Vijay K. Kuchroo
The host-derived regulatory network that controls mucus secretion and thereby changes gut microbiota has not been fully illustrated. Here, we identify that Forkhead box protein O1 (Foxo1) is critical for gut commensalism and intestinal barrier integrity by regulating goblet cell function.

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Current Issue
Volume 218,
Issue 7,
July 5, 2021
Reviews & Opinions
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.
Review | Neuro-Immune Interactions Focus
Yun Chen, Marco Colonna
scRNA-seq analyses of microglial responses to AD pathology in patients and mouse models have provided fundamental insights but also exposed some heterogeneity and discrepancies. Here, we identify consistent microglial response patterns and discuss parallels and incongruities between humans and mice.

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