Immunology

Histone H3 clipping is a novel signature of human neutrophil extracellular traps

1. Dorothea Ogmore Tilley
2. Ulrike Abuabed
3. Ursula Zimny Arndt
4. Monika Schmid
5. Stefan Florian
6. Peter R Jungblut
7. Volker Brinkmann
8. Alf Herzig
9. Arturo Zychlinsky

• Curated by eLife

  Evaluation Summary:

  This study describes a new antibody to identify human neutrophil extracellular traps (NETs) also in tissue samples. The paper might not only introduce an important novel tool for many areas of biomedical research, but it also touches cell biological questions of importance. The usefulness of the NET-specific antibody is impressively developed in the paper, while the mechanistic concepts are not yet fully established.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

The cytokine receptor DR3 identifies and activates thymic NKT17 cells

1. Shunqun Luo
2. Nurcin Liman
3. Assiatu Crossman
4. Jung-Hyun Park

• Curated by eLife

  Evaluation Summary:

  The manuscript by Luo et al. showed that the cytokine receptor DR3 is selectively expressed on thymic NKT17 cells and DR3 ligation leads to the activation of NKT17 cells in the thymus. Overall, The presented experiment are properly executed, controlled and presented. The finding that DR3 acts as a costimulatory molecule for thymic NKT17 cells is interesting. The mechanism and the functional relevance of this finding remain wanting.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife

Predicting T Cell Receptor Antigen Specificity From Structural Features Derived From Homology Models of Receptor-Peptide-Major Histocompatibility Complexes

1. Martina Milighetti
2. John Shawe-Taylor
3. Benny Chain

• Curated by eLife

  Evaluation Summary:

  This manuscript reports a new approach to the important and challenging problem of predicting T cell receptor:peptide-MHC interactions, one that relies on molecular model building (with previously published tools) followed by feature extraction and machine learning. The strengths of the study are more conceptual than practical: the overall framework and analytical approach; a balanced, critical assessment of the method's performance (which does not shy away from negative results); some observations on TCR:pMHC docking geometry. On the practical side, the classifier does not appear to generalize well to unseen epitopes (neither do the published tools it's compared to), so at the end of the day it's not clear that it will be preferable to simpler sequence-based approaches.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Inhibitory IL-10-producing CD4+ T cells are T-bet-dependent and facilitate cytomegalovirus persistence via coexpression of arginase-1

1. Mathew Clement
2. Kristin Ladell
3. Kelly L Miners
4. Morgan Marsden
5. Lucy Chapman
6. Anna Cardus Figueras
7. Jake Scott
8. Robert Andrews
9. Simon Clare
10. Valeriia V Kriukova
11. Ksenia R Lupyr
12. Olga V Britanova
13. David R Withers
14. Simon A Jones
15. Dmitriy M Chudakov
16. David A Price
17. Ian R Humphreys

• Curated by eLife

  Evaluation Summary:

  This manuscript analyses the inhibitory role of IL-10 producing regulatory T-cells in a mouse cytomegalovirus infection model. The authors report that IL-10 producing CD4+T-cells express genes of chronically activated Th1-cells, are clonally expanded and inhibit anti-viral T-cell responses via arginase, an enzyme that breaks down an essential amino acid for T-cell activation. The manuscript presents some novel and potentially important data; however, it requires the provision of additional experimental data and clarifications.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Epigenetic remodeling by vitamin C potentiates plasma cell differentiation

1. Heng-Yi Chen
2. Ana Almonte-Loya
3. Fang-Yun Lay
4. Michael Hsu
5. Eric Johnson
6. Edahí González-Avalos
7. Jieyun Yin
8. Richard S Bruno
9. Qin Ma
10. Hazem E Ghoneim
11. Daniel J Wozniak
12. Fiona E Harrison
13. Chan-Wang Jerry Lio

• Curated by eLife

  Evaluation Summary:

  This manuscript described a role of Vitamin C in promoting plasma cell differentiation by remodeling the epigenome via TET (Ten Eleven Translation) family proteins. Overall, most of experiments are properly executed, controlled and presented. This paper will be of interest to scientists in molecular immunologists, particularly those involved in of epigenetic mechanisms of B cell differentiation to plasma cells.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife

Cytotoxic CD4+ T cells driven by T-cell intrinsic IL-18R/MyD88 signaling predominantly infiltrate Trypanosoma cruzi-infected hearts

1. Carlos-Henrique D Barbosa
2. Fábio B Canto
3. Ariel Gomes
4. Layza M Brandao
5. Jéssica R Lima
6. Guilherme A Melo
7. Alessandra Granato
8. Eula GA Neves
9. Walderez O Dutra
10. Ana-Carolina Oliveira
11. Alberto Nóbrega
12. Maria Bellio

• Curated by eLife

  Evaluation Summary:

  This is an interesting study, conducted in mice, that demonstrates for the first time the presence of a large population of cytotoxic CD4+ T lymphocytes in infection with Trypanosoma cruzi, a relevant human pathogen. At present, the relevance of these cells in protective immunity engendered by the host remains unclear. Additional experiments are needed to characterize the functionality of these cytotoxic CD4 T cells vis-a-vis the canonical Th1 T cells. This paper can be of interest to scientists interested in immune responses to parasitic infections.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife

Transcriptome network analysis implicates CX3CR1-positive type 3 dendritic cells in non-infectious uveitis

1. Sanne Hiddingh
2. Aridaman Pandit
3. Fleurieke Verhagen
4. Rianne Rijken
5. Nila Hendrika Servaas
6. Rina CGK Wichers
7. Ninette H ten Dam-van Loon
8. Saskia M Imhof
9. Timothy RDJ Radstake
10. Joke H de Boer
11. Jonas JW Kuiper

• Curated by eLife

  Evaluation Summary:

  The authors provide evidence suggesting the gene expression profile of a specific subset of dendritic cells define features of specific forms of non-infectious uveitis. This work suggests specific pathways in these cells that may have mechanistic import in inflammatory eye disease. This manuscript is of interested to immunologists studying autoimmunity and ocular immunity. While the paper is largely descriptive, the data it presents should serve as a valuable resource for generating hypotheses about the pathogenesis of ocular autoimmune disease.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

Analysis of allelic cross-reactivity of monoclonal IgG antibodies by a multiplexed reverse FluoroSpot assay

1. Henriette Hoffmann-Veltung
2. Nsoh Godwin Anabire
3. Michael Fokuo Ofori
4. Peter Janhmatz
5. Niklas Ahlborg
6. Lars Hviid
7. Maria del Pilar Quintana

• Curated by eLife

  Evaluation Summary:

  This manuscript describes a fluorospot-based assay as a model for a methodical, step-wise and rigorous approach - that combines multiple reagents in a complex system - to study the cross-reactivity of antibody to polymorphic antigens using the malaria vaccine candidate, VAR2CSA, as a model. The authors apply monoclonal antibodies and the corresponding B cells to validate their multiplexed assay before testing small number of samples from malaria exposed donors in a pilot application of the assay. The data support the conclusions. This information will attract the attention of immunologists and vaccinologists, who are primarily but not exclusively, involved in research on malaria.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

Engineered natural killer cells impede the immunometabolic CD73-adenosine axis in solid tumors

1. Andrea M Chambers
2. Kyle B Lupo
3. Jiao Wang
4. Jingming Cao
5. Sagar Utturkar
6. Nadia Lanman
7. Victor Bernal-Crespo
8. Shadia Jalal
9. Sharon R Pine
10. Sandra Torregrosa-Allen
11. Bennett D Elzey
12. Sandro Matosevic

• Curated by eLife

  Evaluation Summary:

  The authors have engineered an anti-CD73 chimeric antigen receptor (CAR) that they express in NK cells to counteract tumors bearing CD73, which contributes to the generation of immunosuppressive adenosine in the tumor microenvironment. This is a promising approach for a new anti-cancer immunotherapy and will be of interest to oncologists and cancer immunologists. The CAR-bearing NK cells show slightly enhanced tumor killing in vitro, but preliminary data show more promising results in mice. This could be due to the CD73 CAR blocking catalytic activity in the tumor microenvironment more effectively than directly promoting cytotoxicity responses.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

The cIAP ubiquitin ligases sustain type 3 γδ T and innate lymphoid cells during aging to allow normal cutaneous and mucosal responses

1. John Rizk
2. Urs M. Mörbe
3. Rasmus Agerholm
4. Isabel Ulmert
5. Elisa Catafal Tardos
6. Darshana Kadekar
7. Maria V. Baglioni
8. Monica Torrellas Viñals
9. Vasileios Bekiaris

Reviewed by Review Commons