Immunology

Inflammation and IL-4 regulate Parkinson’s and Crohn’s disease associated kinase LRRK2

1. Dina Dikovskaya
2. Rebecca Pemberton
3. Matthew Taylor
4. Anna Tasegian
5. Purbasha Bhattacharya
6. Karolina Zeneviciute
7. Esther M Sammler
8. Andrew J M Howden
9. Dario R Alessi
10. Mahima Swamy

Reviewed by Review Commons

Dynamic chromatin architecture identifies new autoimmune-associated enhancers for IL2 and novel genes regulating CD4+ T cell activation

1. Matthew C Pahl
2. Prabhat Sharma
3. Rajan M Thomas
4. Zachary Thompson
5. Zachary Mount
6. James A Pippin
7. Peter A Morawski
8. Peng Sun
9. Chun Su
10. Daniel Campbell
11. Struan FA Grant
12. Andrew D Wells

• Curated by eLife

  eLife assessment

  This is a solid study that follows a well-established canvas for variant-to-gene prioritisation using 3D genomics, applying it to activated T cells. The authors go some way in validating the lists of candidate genes, as well as exploring the regulatory architecture of a candidate GWAS locus. Jointly with data from previous studies performing variant-to-gene assignment in activated CD4 T cells (and other immune cells), this work provides a useful additional resource for interpreting autoimmune disease-associated genetic variation.

Reviewed by eLife

Direct pharmacological AMPK activation inhibits mucosal SARS-CoV-2 infection by reducing lipid metabolism, restoring autophagy flux and the type I IFN response

1. Andrea Cottignies-Calamarte
2. Flora Marteau
3. Feifan He
4. Sandrine Belouzard
5. Jean Dubuisson
6. Daniela Tudor
7. Benoit Viollet
8. Morgane Bomsel

Reviewed by Review Commons

Lymphoid origin of intrinsically activated plasmacytoid dendritic cells in mice

1. Alessandra Machado Araujo
2. Joseph D Dekker
3. Kendra Garrison
4. Zhe Su
5. Catherine Rhee
6. Zicheng Hu
7. Bum-Kyu Lee
8. Daniel Osorio
9. Jiwon Lee
10. Vishwanath R Iyer
11. Lauren IR Ehrlich
12. George Georgiou
13. Gregory Ippolito
14. Stephen Yi
15. Haley O Tucker

• Curated by eLife

  eLife assessment

  This valuable study reports that while most plasmacytoid dendritic cells (pDCs) originate from common dendritic cell precursors, approximately 20% are derived from lymphoid progenitors shared with B cells. The methodology used and the evidence are solid, and further demonstrate the distinct transcription factor requirements and activities of this subset of pDCs, although the functional significance of this dendritic cell subset will require further elucidation. The findings will be of great interest for those interested in the developmental and functional biology of the immune system.

Reviewed by eLife

SLAM/SAP signaling regulates discrete γδ T cell developmental checkpoints and shapes the innate-like γδ TCR repertoire

1. Somen K Mistri
2. Brianna M Hilton
3. Katherine J Horrigan
4. Emma S Andretta
5. Remi Savard
6. Oliver Dienz
7. Kenneth J Hampel
8. Diana L Gerrard
9. Joshua T Rose
10. Nikoletta Sidiropoulos
11. Dev Majumdar
12. Jonathan E Boyson

• Curated by eLife

  eLife assessment

  This important study highlights the importance of SLAM-SAP signaling in determining innate gamma-delta T cell sublineages and their T cell receptor repertoires. It uncovers the complex role of the SLAM-SAP pathway in developing specific gamma-delta T cell subsets. The evidence presented is compelling, backed by high-quality data obtained through advanced single cell proteogenomics techniques.This work will be of broad interest to immunologists.

Reviewed by eLife

Vangl2 suppresses NF-κB signaling and ameliorates sepsis by targeting p65 for NDP52-mediated autophagic degradation

1. Jiansen Lu
2. Jiahuan Zhang
3. Huaji Jiang
4. Zhiqiang Hu
5. Yufen Zhang
6. Lian He
7. Jianwu Yang
8. Yingchao Xie
9. Dan Wu
10. Hongyu Li
11. Ke Zeng
12. Peng Tan
13. Qingyue Xiao
14. Zijing Song
15. Chenglong Pan
16. Xiaochun Bai
17. Xiao Yu

• Curated by eLife

  eLife assessment

  This valuable manuscript describes a novel role of Vangl2, a core planar cell polarity protein, in linking the NF-kB pathway to selective autophagic protein degradation in myeloid cells. The mechanistic studies provide convincing evidence that Vangl2 targets p65 for NDP52-mediated autophagic degradation, limiting inflammatory NF-kB response, with functional significance of the proposed mechanism in sepsis. Additional future studies dissecting autophagic Vangl2 functions in various myeloid subsets in the context of inflammation could be informative, and additional Vangl2 targets in the inflammatory pathway, including IKK2, could also be explored. Overall, this exciting study can advance our understanding of NF-kB control, particularly in the context of inflammatory diseases.

Reviewed by eLife

An arms race between 5’ppp-RNA virus and its alternative recognition receptor MDA5 in RIG-I-lost teleost fish

1. Shang Geng
2. Xing Lv
3. Weiwei Zheng
4. Tianjun Xu

• Curated by eLife

  eLife assessment

  This important study shows that in teleost fish, the RIG-I-like protein MDA5 can compensate for the absence of RIG-I by detecting 5'-triphosphorylated RNA. A fish virus containing such RNA can nevertheless evade MDA5 detection through a mechanism involving m6A methylation-induced silencing. The conclusions, which are supported by solid data, advance our understanding of antiviral immunity and virus-host conflicts in vertebrates.

Reviewed by eLife

Single-cell transcriptome and T cell receptor profiling of the tuberculin skin test

1. Carolin T. Turner
2. Joshua Rosenheim
3. Clare Thakker
4. Aneesh Chandran
5. Holly Wilson
6. Cristina Venturini
7. Gabriele Pollara
8. Benjamin M. Chain
9. Gillian S. Tomlinson
10. Mahdad Noursadeghi

Reviewed by PREreview

The bacterial quorum sensing signal 2’-aminoacetophenone rewires immune cell bioenergetics through the Ppargc1a/Esrra axis to mediate tolerance to infection

1. Arijit Chakraborty
2. Arunava Bandyopadhaya
3. Vijay K Singh
4. Filip Kovacic
5. Sujin Cha
6. William M Oldham
7. A Aria Tzika
8. Laurence G Rahme

• Curated by eLife

  eLife assessment

  This important study demonstrates that the Pseudomonas aeruginosa-derived quorum sensing signal, 2-aminoacetophenone, induces immune tolerization in macrophages by perturbing metabolism, particularly in the context of mitochondrial respiration and bioenergetics. The authors present convincing evidence for 2-aminoacetophenone-mediated reduction of pyruvate transport into mitochondria, with downstream effects that result in reduced ATP production in tolerized macrophages. The work will be of interest to those studying host-pathogen interactions.

Reviewed by eLife

Enkephalin-mediated modulation of basal somatic sensitivity by regulatory T cells in mice

1. Nicolas Aubert
2. Madeleine Purcarea
3. Julien Novarino
4. Julien Schopp
5. Alexis Audibert
6. Wangtianrui Li
7. Marie Fornier
8. Léonie Cagnet
9. Marie Naturel
10. Armanda Casrouge
11. Marie-Caroline Dieu-Nosjean
12. Nicolas Blanchard
13. Gilles Dietrich
14. Cedric Peirs
15. Gilles Marodon

• Curated by eLife

  eLife assessment

  This study presents a valuable finding on a new role of Foxp3+ regulatory T cells in sensory perception, which may have an impact on our understanding of somatosensory perception. The authors identified a previously unappreciated action of enkephalins released by immune cells in the resolution of pain and several upstream signals that can regulate the expression of the proenkephalin gene PENK in Foxp3+ Tregs. The generation of transgenic mice with conditional deletion of PENK in Foxp3+ cells and PENK fate-mapping is novel and generates compelling data; they also show a comprehensive analysis of Tregs in control and transgenic mice, longitudinal data on heat sensitivity and co-localization of PENK+ Tregs with thermal sensory neurons in the skin further supporting their hypothesis. The study would be of interest to the biologists working in the field of neuroimmunology and inflammation.

Reviewed by eLife