Immunology

Developmental conversion of thymocyte-attracting cells into self-antigen-displaying cells in embryonic thymus medulla epithelium

1. Izumi Ohigashi
2. Andrea J White
3. Mei-Ting Yang
4. Sayumi Fujimori
5. Yu Tanaka
6. Alison Jacques
7. Hiroshi Kiyonari
8. Yosuke Matsushita
9. Sevilay Turan
10. Michael C Kelly
11. Graham Anderson
12. Yousuke Takahama

• Curated by eLife

  eLife assessment

  This important study provides new insights into the development and function of medullary thymus epithelial cells (mTEC). The authors provide compelling evidence to support their claims as to the differentiation and lineage outcomes of CCL21+ mTEC progenitors, which further our understanding of how central tolerance of T cells is enforced within the thymus.

Reviewed by eLife

The interferon-rich skin environment regulates Langerhans cell ADAM17 to promote photosensitivity in lupus

1. Thomas Morgan Li
2. Victoria Zyulina
3. Ethan S Seltzer
4. Marija Dacic
5. Yurii Chinenov
6. Andrea R Daamen
7. Keila R Veiga
8. Noa Schwartz
9. David J Oliver
10. Pamela Cabahug-Zuckerman
11. Jose Lora
12. Yong Liu
13. William D Shipman
14. William G Ambler
15. Sarah F Taber
16. Karen B Onel
17. Jonathan H Zippin
18. Mehdi Rashighi
19. James G Krueger
20. Niroshana Anandasabapathy
21. Inez Rogatsky
22. Ali Jabbari
23. Carl P Blobel
24. Peter E Lipsky
25. Theresa T Lu

• Curated by eLife

  eLife assessment

  This study presents a useful assessment of the possible role of type I interferons in inhibiting Adam17 protease/sheddase activity and their correlation with decreased Langerhans Cells signature in lesional and nonlesional CLE and murine models as cause of photosensitive lupus. The data were collected and analyzed using a solid methodology. This work will be of interest to scientists interested in photosensitivity in the setting of lupus.

Reviewed by eLife

ER-to-lysosome Ca2+ refilling followed by K+ efflux-coupled store-operated Ca2+ entry in inflammasome activation and metabolic inflammation

1. Hyereen Kang
2. Seong Woo Choi
3. Joo Young Kim
4. Soo-Jin Oh
5. Sung Joon Kim
6. Myung-Shik Lee

• Curated by eLife

  eLife assessment

  This useful study proposes a role of lysosomal Ca2+ release in inflammasome signaling and metabolic inflammation. While the proposed model would be of considerable interest to the field of immunology if validated, the experimental approaches to study calcium dynamics are problematic, with one of several concerns being the transfection efficiency. The major claims of the paper are thus only incompletely supported.

Reviewed by eLife

Caspase-1 activates gasdermin A in non-mammals

1. Zachary Paul Billman
2. Stephen Bela Kovacs
3. Bo Wei
4. Kidong Kang
5. Ousmane H Cissé
6. Edward A Miao

• Curated by eLife

  eLife assessment

  This study presents valuable insights into the evolution of the gasdermin family, making a strong case that a GSDMA-like gasdermin activated by caspase-1 cleavage was already present in early land vertebrates. Convincing biochemical evidence is provided that extant avian, reptilian, and amphibian GSDMA proteins can still be activated by caspase-1 and upon cleavage induce pyroptosis-like cell death -- at least that they do so in the context of human cell lines. The caspase-1 cleavage site has only been lost in mammals, which use the more recently evolved GSDMD as a caspase-1 cleavable pyroptosis inducer. The presented work will be of considerable interest to scientists working on the evolution of cell death pathways, or on cell death regulation in non-mammalian vertebrates.

Reviewed by eLife

Murine alveolar macrophages rapidly accumulate intranasally administered SARS-CoV-2 Spike protein leading to neutrophil recruitment and damage

1. Chung Park
2. Il-Young Hwang
3. Serena Li-Sue Yan
4. Sinmanus Vimonpatranon
5. Danlan Wei
6. Don Van Ryk
7. Alexandre Girard
8. Claudia Cicala
9. James Arthos
10. John H Kehrl

• Curated by eLife

  eLife assessment

  This paper investigates the impact of intranasal instillation of SARS CoV2 spike protein in mouse models of lung inflammation. The authors conclude that the spike protein can interact with macrophages through carbohydrate recognition and can induce recruitment and NETosis of neutrophils, contributing to lung inflammation. They also use the cremaster muscle model to investigate effect of the spike proteins on neutrophil dynamics and death using intravital microscopy. Given that mucosal vaccines using SARS CoV2 spike variants could be envisioned as desirable, the observation that spike can induce lung/mucosal inflammation even without an adjuvant is important. Despite limitations of some loose terminology and some weak controls, the key observations are solid and demand further attention given the importance of the antigen.

Reviewed by eLife

RBP-J regulates homeostasis and function of circulating Ly6Clo monocytes

1. Tiantian Kou
2. Lan Kang
3. Bin Zhang
4. Jiaqi Li
5. Baohong Zhao
6. Wenwen Zeng
7. Xiaoyu Hu

• Curated by eLife

  eLife assessment

  This study presents a valuable examination into the role Notch-RBP-J signalling in regulating monocyte subset homeostasis. The data were collected and analysed using solid and validated methodology and can be used as a starting point for exploring the mechanisms involved in RBP-J signalling in non-classical monocytes. The data presented strongly confirm the authors conclusions. However, this paper primarily focuses on providing a description, and additional studies are necessary to fully elucidate the mechanisms through which RBP-J deficiency contributes to the specific increase in Ly6Clo monocyte numbers in both the blood and lungs.

Reviewed by eLife

Neuronal NPR-15 modulates molecular and behavioral immune responses via the amphid sensory neuron-intestinal axis in C. elegans

1. Benson Otarigho
2. Anna Frances Butts
3. Alejandro Aballay

• Curated by eLife

  eLife assessment

  The important work by Aballay et al. significantly advances our understanding of how G protein-coupled receptors (GPCRs) regulate immunity and pathogen avoidance. The authors provide convincing evidence for the GPCR NPR-15 to mediate immunity by altering the activity of several key transcription factors. This work will be of broad interest to immunologists.

Reviewed by eLife

Stimulation-induced cytokine polyfunctionality as a dynamic concept

1. Kevin Portmann
2. Aline Linder
3. Klaus Eyer

• Curated by eLife

  eLife assessment

  This useful study uses a microfluidic method to evaluate the ability of single human white blood cells to produce combinations of cytokines and the evidence that this takes place is solid. The paper highlights polyfunctionality using data that are similar to a prior dataset from the same group. The authors comment that, in analysis of larger panels, single cells rarely make more than 2 or 3 cytokines so that investigation of 3 cytokines at a time is sufficient to investigate this phenomenon. Coupling this approach to other modes of single cell analysis may provide greater insight into what limits simultaneous production of multiple cytokines.

Reviewed by eLife

A specific innate immune response silences the virulence of Pseudomonas aeruginosa in a latent infection model in the Drosophila melanogaster host

1. Jing Chen
2. Guiying Lin
3. Kaiyu Ma
4. Zi Li
5. Samuel Liégeois
6. Dominique Ferrandon

Reviewed by Review Commons

Mast cell activation disrupts interactions between endothelial cells and pericytes during early life allergic asthma

1. Régis Joulia
2. Franz Puttur
3. Helen Stölting
4. William J. Traves
5. Lewis J. Entwistle
6. Anastasia Voitovich
7. Minerva Garcia Martín
8. May Al-Sahaf
9. Katie Bonner
10. Elizabeth Scotney
11. Philip L. Molyneaux
12. Richard J. Hewitt
13. Simone A. Walker
14. Laura Yates
15. Sejal Saglani
16. Clare M. Lloyd

Reviewed by Arcadia Science