Current issue

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Speaking out about gender imbalance in invited speakers improves diversity pp475 - 478

Robyn S Klein, Rhonda Voskuhl, Benjamin M Segal, Bonnie N Dittel, Thomas E Lane, John R Bethea, Monica J Carson, Carol Colton, Susanna Rosi, Aileen Anderson, Laura Piccio, Joan M Goverman, Etty N Benveniste, Melissa A Brown, Seema Kaushalya Tiwari-Woodruff, Tajie H Harris & Anne H Cross


Omissions of qualified women scientists from major meeting programs continue to occur despite a surge in articles indicating persistent gender-discriminatory practices in hiring and promotion, and calls for gender balance in conference organizing committees.


News and Views

IRE1 gives weight to obesity-associated inflammation pp479 - 480

Bojan Bujisic & Fabio Martinon


IRE1α is a stress sensor that is activated by a high-fat diet. In adipose-tissue macrophages, it serves as a major switch toward pro-inflammatory M1 polarization and thereby contributes to obesity and associated diseases.

See also: Article by Shan et al.

The immune system as a social network pp481 - 482

Andreas Bergthaler & Jörg Menche


The immune system employs a multitude of molecules, cells and organs that act together throughout the entire body to guard human health. Much like in a social network, immune cells can exert full functionality only through effective collaboration and communication.

See also: Resource by Rieckmann et al.

Gene-enhancer variants reveal diverse TCR-mediated differentiation pp483 - 484

Michael P Gallagher & Leslie J Berg


The transcription factor IRF4 acts as a 'rheostat' for TCR signaling. Discrete levels of IRF4 can activate distinct transcriptional programs in T cells due to binding sites of variable affinity in groups of target genes.

See also: Article by Iwata et al.

Dietary short-chain fatty acids protect against type 1 diabetes pp484 - 486

Li Wen & F Susan Wong


The short-chain fatty acids (SCFAs) acetate and butyrate, which are released from specialized diets by gut microbes, protect non-obese diabetic (NOD) mice against insulitis and slow the progression of diabetes.

See also: Article by Mariño et al.



Mitochondria are the powerhouses of immunity pp488 - 498

Evanna L Mills, Beth Kelly & Luke A J O'Neill


O’Neill and colleagues review the role of mitochondria dynamics and energetics in immunity and inflammation, in innate and adaptive immune cells.



Long noncoding RNA lncKdm2b is required for ILC3 maintenance by initiation of Zfp292 expression pp499 - 508

Benyu Liu, Buqing Ye, Liuliu Yang, Xiaoxiao Zhu, Guanling Huang, Pingping Zhu, Ying Du, Jiayi Wu, Xiwen Qin, Runsheng Chen, Yong Tian & Zusen Fan


Long noncoding RNAs contribute to the cell-type-specific regulation of gene expression. Fan and colleagues identify a unique conserved lncRNA, lncKdm2b, that is transcribed divergently from the Kdm2b gene and is necessary for ILC3 maintenance in the gut.

IRAP+ endosomes restrict TLR9 activation and signaling pp509 - 518

Joel Babdor, Delphyne Descamps, Aimé Cézaire Adiko, Mira Tohmé, Sophia Maschalidi, Irini Evnouchidou, Luiz Ricardo Vasconcellos, Mariacristina De Luca, Francois-Xavier Mauvais, Meriem Garfa-Traore, Melanie M Brinkmann, Michel Chignard, Bénédicte Manoury & Loredana Saveanu


The receptor TLR9 needs to be carefully regulated to avoid recognition of self nucleic acids and ensuing autoinflammation. Saveanu and colleagues demonstrate a further level of regulation through the retention of TLR9 in IRAP+ endosomes.

The metabolic ER stress sensor IRE1α suppresses alternative activation of macrophages and impairs energy expenditure in obesity pp519 - 529

Bo Shan, Xiaoxia Wang, Ying Wu, Chi Xu, Zhixiong Xia, Jianli Dai, Mengle Shao, Feng Zhao, Shengqi He, Liu Yang, Mingliang Zhang, Fajun Nan, Jia Li, Jianmiao Liu, Jianfeng Liu, Weiping Jia, Yifu Qiu, Baoliang Song, Jing-Dong J Han, Liangyou Rui, Sheng-Zhong Duan & Yong Liu


‘Crown-like’ structures composed of apoptotic adipocytes surrounded by adipose tissue macrophages (ATMs) are a characteristic of obesity. Liu and colleagues show that engulfment of apoptotic adipocytes triggers an ER stress response in ATMs and drives the proinflammatory response that underlies obesity.

See also: News and Views by Bujisic & Martinon

Opposing macrophage polarization programs show extensive epigenomic and transcriptional cross-talk pp530 - 540

Viviana Piccolo, Alessia Curina, Marco Genua, Serena Ghisletti, Marta Simonatto, Arianna Sabò, Bruno Amati, Renato Ostuni & Gioacchino Natoli


Natoli and colleagues reveal the epigenomic and transcriptional bases for gene-specific cross-repression of the cytokines IFN-γ and IL-4 in macrophages.

NLRP12 attenuates colon inflammation by maintaining colonic microbial diversity and promoting protective commensal bacterial growth pp541 - 551

Liang Chen, Justin E Wilson, Mark J Koenigsknecht, Wei-Chun Chou, Stephanie A Montgomery, Agnieszka D Truax, W June Brickey, Christopher D Packey, Nitsan Maharshak, Glenn K Matsushima, Scott E Plevy, Vincent B Young, R Balfour Sartor & Jenny P-Y Ting


The intracellular sensor NLRP12 can negatively regulate inflammation. Ting and colleagues demonstrate that an absence of NLRP12 triggers a dysbiosis that feeds forward into a process of inflammation and colitis.

Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes pp552 - 562

Eliana Mariño, James L Richards, Keiran H McLeod, Dragana Stanley, Yu Anne Yap, Jacinta Knight, Craig McKenzie, Jan Kranich, Ana Carolina Oliveira, Fernando J Rossello, Balasubramanian Krishnamurthy, Christian M Nefzger, Laurence Macia, Alison Thorburn, Alan G Baxter, Grant Morahan, Lee H Wong, Jose M Polo, Robert J Moore, Trevor J Lockett, Julie M Clarke, David L Topping, Leonard C Harrison & Charles R Mackay


The gut microbiota can influence immune-cell function by the production of short-chain fatty acids. Mackay and colleagues show that diets enriched for acetate and butyrate protect non-obese diabetic mice from insulitis and diabetes progression.

See also: News and Views by Wen & Wong

Quality of TCR signaling determined by differential affinities of enhancers for the composite BATF–IRF4 transcription factor complex pp563 - 572

Arifumi Iwata, Vivek Durai, Roxane Tussiwand, Carlos G Briseño, Xiaodi Wu, Gary E Grajales-Reyes, Takeshi Egawa, Theresa L Murphy & Kenneth M Murphy


Murphy and colleagues show that the transcription-factor complex BATF-IRF4, which recognizes AICE motifs within gene enhancers, is sensitive to TCR signaling strength and identify distinct gene targets that respond to graded doses of TCR stimulation.

See also: News and Views by Gallagher & Berg

Epigenetic landscapes reveal transcription factors that regulate CD8+ T cell differentiation pp573 - 582

Bingfei Yu, Kai Zhang, J Justin Milner, Clara Toma, Runqiang Chen, James P Scott-Browne, Renata M Pereira, Shane Crotty, John T Chang, Matthew E Pipkin, Wei Wang & Ananda W Goldrath


Distinct transcription factors influence cell fate, including the generation of effector or memory CD8+ T cells. Goldrath, Wang and colleagues have developed a Page-Rank analysis that shows that the transcription factors YY1 and Nr3c1, which are expressed constitutively, promote the differentiation of effector cells or memory cells, respectively.



Social network architecture of human immune cells unveiled by quantitative proteomics pp583 - 593

Jan C Rieckmann, Roger Geiger, Daniel Hornburg, Tobias Wolf, Ksenya Kveler, David Jarrossay, Federica Sallusto, Shai S Shen-Orr, Antonio Lanzavecchia, Matthias Mann & Felix Meissner


Immune cells give rise to the most interconnected system in the body. Meissner and colleagues perform comprehensive proteomics and secretomics to describe in detail the ‘social network’ of human immune cells and throw light on previously unknown cell connectivities.

See also: News and Views by Bergthaler & Menche