Immunology

Structure-based prediction of T cell receptor:peptide-MHC interactions

1. Philip Bradley

• Curated by eLife

  eLife assessment

  The author customises an alpha-fold multimer neural network to predict TCR-pMHC and applies this to the problem of identifying peptides from a limited library, that might engage TCR with a known sequence from a limited list of potential peptides. This is an important structural problem and a useful step that can be further improved through better metrics, comparison to existing approaches, and consideration of the sensitivity of the recognition processes to small changes in structure.

Reviewed by eLife

Single-cell analysis of the aged ovarian immune system reveals a shift towards adaptive immunity and attenuated cell function

1. Tal Ben Yaakov
2. Tanya Wasserman
3. Eliel Aknin
4. Yonatan Savir

• Curated by eLife

  eLife assessment

  The study by Ben Yaakov et al. describes a single cell analysis of the mammalian ovary in young, adult and old mice. Based on gene expression profiles, the authors identified cell clusters corresponding to immune cell populations in mouse ovaries and compared their abundance in aged compared to adult animals. In comparison with previous studies that used single cell RNAseq to characterize the heterogeneity of cell types in the ovary, this study focuses only on immune cells resulting in much better coverage to characterize the changes that these cells undergo as a function of age. The combination of single-cell RNA sequencing and flow cytometry used by the authors is a robust and unbiased approach to characterize immune cell alterations in aging ovaries. Overall, the data and analyses presented in this study reveal profound modifications of the immune system in the aging reproductive system in mice. However, while both the data and biology presented are quite interesting, this study is perhaps too wide in breadth such that no individual result is extensively and rigorously explored.

Reviewed by eLife

Regulatory T cells suppress the formation of potent KLRK1 and IL-7R expressing effector CD8 T cells by limiting IL-2

1. Oksana Tsyklauri
2. Tereza Chadimova
3. Veronika Niederlova
4. Jirina Kovarova
5. Juraj Michalik
6. Iva Malatova
7. Sarka Janusova
8. Olha Ivashchenko
9. Helene Rossez
10. Ales Drobek
11. Hana Vecerova
12. Virginie Galati
13. Marek Kovar
14. Ondrej Stepanek

• Curated by eLife

  eLife assessment

  This manuscript is of primary interest to immunologists with a focus on the effects of interleukin-2 and T cell receptor (TCR) signaling on effector T cell differentiation and function. Extensive and well-controlled experiments support a model where TCR and interleukin-2 signals promote a specific subset of effector CD8+ T cells - termed KILR cells - with superior target cell killing properties.

Reviewed by eLife

Human Dectin-1 is O-glycosylated and serves as a ligand for C-type lectin receptor CLEC-2

1. Shojiro Haji
2. Taiki Ito
3. Carla Guenther
4. Miyako Nakano
5. Takashi Shimizu
6. Daiki Mori
7. Yasunori Chiba
8. Masato Tanaka
9. Sushil K Mishra
10. Janet A Willment
11. Gordon D Brown
12. Masamichi Nagae
13. Sho Yamasaki

• Curated by eLife

  eLife assessment

  The C-type lectin receptor family recognise pathogens and self-components. Dectin-1 is known to recognize glucan on pathogens. In this fundamental study Dectin-1 and CLEC-2 another - C-type lectin receptor, expressed on platelets - interact through an O-glycosylated ligand presented in the stalk region of Dectin-1. This compelling study demonstrates a potential role for pattern recognition receptors in physiological processes.

Reviewed by eLife

Plasmodium infection disrupts the T follicular helper cell response to heterologous immunization

1. Mary F Fontana
2. Erica Ollmann Saphire
3. Marion Pepper

• Curated by eLife

  eLife assessment

  Malaria is still one of the world's most deadly diseases because our bodies cannot make appropriate acquired immunity upon Plasmodium infection (the causative agent of malaria). By using animal models of malaria infection and vaccination, this important work shows that Dendritic cells (DCs) have a lower ability to uptake Plasmodium-infected RBCs (particle antigen). This DC dysfunction could be an important reason behind T cell dysfunction in Plasmodium infection. The data presented here convincingly supports the conclusions.

Reviewed by eLife

Compartmentalization and persistence of dominant (regulatory) T cell clones indicates antigen skewing in juvenile idiopathic arthritis

1. Gerdien Mijnheer
2. Nila Hendrika Servaas
3. Jing Yao Leong
4. Arjan Boltjes
5. Eric Spierings
6. Phyllis Chen
7. Liyun Lai
8. Alessandra Petrelli
9. Sebastiaan Vastert
10. Rob J de Boer
11. Salvatore Albani
12. Aridaman Pandit
13. Femke van Wijk

• Curated by eLife

  eLife assessment

  In this study, the authors performed mass cytometry (CyTOF) analysis and T cell receptor (TCR) sequencing to study immune cell composition and expansion of joint-derived Tregs and non-Tregs in Juvenile Idiopathic Arthritis (JIA). They studied different joints affected at the same time and found that the composition and functional characteristics of immune infiltrates are strikingly similar between joints within one patient. The research design of this study is appropriate and the methods used in this study are adequately described in the manuscript. The study may be potentially beneficial for the JIA treatment.

Reviewed by eLife

The Toll pathway mediates Drosophila resilience to Aspergillus mycotoxins through specific Bomanins

1. Rui Xu
2. Yanyan Lou
3. Antonin Tidu
4. Philippe Bulet
5. Thorsten Heinekamp
6. Franck Martin
7. Axel Brakhage
8. Zi Li
9. Samuel Liégeois
10. Dominique Ferrandon

Reviewed by Review Commons

Succinate mediates inflammation-induced adrenocortical dysfunction

1. Ivona Mateska
2. Anke Witt
3. Eman Hagag
4. Anupam Sinha
5. Canelif Yilmaz
6. Evangelia Thanou
7. Na Sun
8. Ourania Kolliniati
9. Maria Patschin
10. Heba Abdelmegeed
11. Holger Henneicke
12. Waldemar Kanczkowski
13. Ben Wielockx
14. Christos Tsatsanis
15. Andreas Dahl
16. Axel Karl Walch
17. Ka Wan Li
18. Mirko Peitzsch
19. Triantafyllos Chavakis
20. Vasileia Ismini Alexaki

• Curated by eLife

  eLife assessment

  Acute inflammation in mammals activates the hypothalamic pituatary axis leading to increased glucocorticoid release, which is required to restrain the inflammatory response. However, in settings of severe or prolonged inflammation, such as that seen in sepsis, there is reduced adrenal steridogenesis. The studies described in this paper provide a plausible mechanism for adrenal resistance which develops during excessive inflammation.

Reviewed by eLife

Cell circuits between leukemic cells and mesenchymal stem cells block lymphopoiesis by activating lymphotoxin beta receptor signaling

1. Xing Feng
2. Ruifeng Sun
3. Moonyoung Lee
4. Xinyue Chen
5. Shangqin Guo
6. Huimin Geng
7. Marcus Müschen
8. Jungmin Choi
9. Joao Pedro Pereira

• Curated by eLife

  eLife assessment

  This study describes a previously unrecognized positive feedback loop between leukemic cells and stromal cells impeding normal hematopoiesis mediated by lymphotoxin produced by cancer cells and its receptor expressed in stromal cells. These valuable findings will guide future research in both basic and clinical medicine. However, additional experimental evidence including more comparator groups would have further substantiated the authors' conclusions.

Reviewed by eLife

Transiently heritable fates and quorum sensing drive early IFN-I response dynamics

1. Laura C Van Eyndhoven
2. Vincent PG Verberne
3. Carlijn VC Bouten
4. Abhyudai Singh
5. Jurjen Tel

• Curated by eLife

  eLife assessment

  This study presents a valuable finding that adds to a growing body of evidence reporting heritable cell states that can guide fate choices in single cells, in this case the fate of early IFN-I response. The evidence supporting the claims of the authors is solid, although testing the generalizability of the result to other cell types or contexts and strengthening the link to epigenetic regulation would have strengthened the study. Overall, this work will be of interest to a wide set of scientists, including cell biologists, immunologists, and systems biologists.

Reviewed by eLife