Immunology

The 1000+ mouse project: large–scale spatiotemporal parametrization and modeling of preclinical cancer immunotherapies

1. Adam L Kenet
2. Sooraj Achar
3. Alka Dwivedi
4. John Buckley
5. Marie Pouzolles
6. Haiying Qin
7. Christopher Chien
8. Naomi Taylor
9. Grégoire Altan-Bonnet

• Curated by eLife

  eLife Assessment

  The authors developed a fundamental computational method, which is intended to automatically process bioluminescence imaging-derived tumour images across anatomical regions and over time. This allows quantitative analysis of such data, and the authors applied it to describe the spatiotemporal distribution of tumour cells in response to CD19-targeted CAR-T cells that contained either CD28 or 4-1BB costimulatory domains. Some operational limitations were identified, which relate to the pipeline's reliance on predefined regions of interest instead of aligning signal sites with anatomical information, scaling, and limitations in taking animal pose into account. Overall, the authors provide compelling evidence for the functionality of their computational approach towards automated analysis of bioluminescence imaging data, while applying it to a current topic of wide interest in cell therapy research.

Reviewed by eLife

Cas9 ⁺ conditionally immortalized neutrophil progenitors as a tool for genome wide CRISPR screening for neutrophil differentiation and function

1. Robyn M. Jong
2. Krystal L. Ching
3. Nicholas E. Garelis
4. Alex Zilinskas
5. Xammy Nguyenla
6. Sagar Rawal
7. Bianca C. Hill
8. Bridget A. Luckie
9. Lillian Shallow
10. Jeffery S. Cox
11. Gregory M. Barton
12. Sarah A. Stanley

• Curated by eLife

  eLife Assessment

  In this manuscript, Jong et al. provide and validate a very useful resource for performing CRISPR screenings to study neutrophil differentiation and function by generating Hoxb8 cells that constitutively express Cas9. This library-screening approach has the potential to improve on the established lentiviral CRISPR-Cas9 editing of Hoxb8 cells. However, the technical advances provided are only incremental and the results presented in this study do not significantly further our understanding of these cells, but rather provide a good validation of their Cas9+ modified version.

Reviewed by eLife

Predestined neutrophil heterogeneity in homeostasis varies in transcriptional and phenotypic response to Candida

1. Allison K. Scherer
2. Alex Hopke
3. Shuying Xu
4. Adam Viens
5. Natalie J. Alexander
6. Kyle D. Timmer
7. Dakota Archambault
8. Daniel Floyd
9. Natalie J. Atallah
10. Catherine Rhee
11. Murat Cetinbas
12. David T. Scadden
13. Daniel Irimia
14. David B. Sykes
15. Ruslan I. Sadreyev
16. Michael K. Mansour

• Curated by eLife

  eLife Assessment

  In their study, Scherer and colleagues aim to use analyses of single-cell clones of murine granulocyte monocyte progenitors that are conditionally immortalized, and analyses of neutrophils derived from those clones to characterize an experimental system for studying neutrophil heterogeneity. The multi-omic and functional analyses reported are valuable but the strength of the evidence presented in support of them is incomplete because the study lacks a rigorous demonstration that the neutrophil-like cells that they derive are fully mature neutrophils.

Reviewed by eLife

Tolerance to Lung Infection in TWIK2 K+ Efflux Mediated Macrophage Trained Immunity

1. Josh Thompson
2. Yufan Li
3. Yuanling Song
4. Anas Anas
5. Jaewon Cho
6. Ki-Wook Kim
7. Asrar B Malik
8. Jingsong Xu

• Curated by eLife

  eLife Assessment

  This study presents valuable data suggesting that ATP-induced modulation of alveolar macrophage (AM) functions is associated with NLRP3 inflammasome activation and enhanced phagocytic capacity. While the in vivo and in vitro data reveal an interesting phenotype, the evidence provided is incomplete and does not fully support the paper's conclusions. Additional investigations would be of value in complementing the data and strengthening the interpretation of the results. This study should be of interest to immunologists and the mucosal immunity community.

Reviewed by eLife

TGF-β drives the conversion of conventional NK cells into uterine tissue-resident NK cells to support murine pregnancy

1. Josselyn D Barahona
2. Liping Yang
3. D Michael Nelson
4. Wayne M Yokoyama

• Curated by eLife

  eLife Assessment

  The importance of uterine natural killer (NK) cells in reproductive success has been demonstrated in mice and humans; however, it is still unclear how uterine NK cells are developed. In this valuable manuscript, the authors provide convincing evidence that TGF-b signaling in NK cells supports normal pregnancy in mice by the conversion of conventional NK cells into uterine tissue-resident NK cells. There are some concerns about the paper, particularly around Figures 1A, 1C, and 2E.

Reviewed by eLife

An IL-21R hypomorph circumvents functional redundancy to define STAT1 signaling in germinal center responses

1. Christoph Jandl
2. Joanna Warren
3. Samantha Owens
4. Marcel Batten
5. Howard Wang
6. Cecile King

• Curated by eLife

  eLife Assessment

  IL21R, being a key cytokine receptor for shaping the T follicular helper and B cell functions, utilizes two STAT family members, STAT1 and STAT3. The authors utilize the IL21R ENU-induced mutant, together with relevant in vitro and in vivo experiments, to dissect the function of STAT1 and STAT3. The approach by itself sounds reasonable, but the main conclusions are incompletely supported by the data presented in this manuscript.

Reviewed by eLife

Innate immune responses to Plasmodium falciparum disrupt the blood-brain barrier

1. Alina Batzilla
2. Pia Dernick
3. Jon Bezney
4. Andreas R. Gschwind
5. Fumio Nakaki
6. Mireia Altadill
7. Hannah Fleckenstein
8. Livia Piatti
9. Silvia Sanz Sender
10. Manuel Fiegl
11. Olawunmi Rashidat Oyerinde
12. Borja Lopez Gutierrez
13. Miguel Lopez-Botet
14. James Sharpe
15. Lars Steinmetz
16. Gemma Moncunill
17. Maria Bernabeu

Reviewed by Rapid Reviews Infectious Diseases

Drosophila host defense mechanisms against filamentous fungal pathogens with diverse lifestyles

1. Guiqing Liu
2. Yao Tian
3. Mark Austin Hanson
4. Prince Kumar Sah
5. Jun Li
6. Bruno Lemaitre

Reviewed by Review Commons

The long non-coding RNA Dreg1 is required for optimal ILC2 development

1. Sara Quon
2. Adelynn Tang
3. Nadia Iannarella
4. Kael Schoffer
5. Wing Fuk Chan
6. Timothy M Johanson
7. Ajithkumar Vasanthakumar
8. Rhys S Allan

• Curated by eLife

  eLife Assessment

  This is a useful study that investigates the role of the long non-coding RNA Dreg1 for the development, differentiation, or maintenance of group 2 ILC (ILC2). The authors generate Dreg1-/- mice and show a reduction of group 2 innate lymphoid cells (ILC2). However, the strength of evidence supporting the impact of Dreg1 on Gata3 expression, a transcription factor required for ILC2 cell fate decisions, and the cell-intrinsic requirement of Dreg1 for ILC2 remain incomplete. This study will be of interest to immunologists.

Reviewed by eLife

PDL-1+ Neutrophils mediate susceptibility during endotoxemia in Metabolically Dysfunctional-Associated Fatty Liver Disease

1. Cleyson da Cruz Oliveira Barros
2. Alexandre Kanashiro
3. Gabriel Victor Lucena da Silva
4. Paulo Sérgio de Almeida Augusto
5. Guilherme Cesar Martelossi Cebinelli
6. Luiz Osório Leiria
7. Thiago Mattar Cunha
8. José Carlos Alves Filho
9. Fernando Queiroz Cunha

• Curated by eLife

  eLife Assessment

  This valuable study highlights the key role of NK cells and PD-L1+ neutrophils in worsening sepsis responses in the context of MASH (metabolic dysfunction-associated steatohepatitis). It focused on the role of neutrophils in mediating this effect, which is based on a choline-deficient high-fat diet model of various knockouts or selective ablation of immune cell types. While the data presented are of great interest, there are concerns around the reliability of the strength of the evidence provided, which is currently considered incomplete. The study may be of interest to researchers in immunopathological disease mechanisms once confirmatory studies have been completed.

  [Editors' note: the authors no longer have access to the original flow cytometry data and plan to compile new datasets for further consideration.]

Reviewed by eLife