Immunology and Inflammation

Cell-autonomous targeting of arabinogalactan by host immune factors inhibits mycobacterial growth

1. Lianhua Qin
2. Junfang Xu
3. Jianxia Chen
4. Sen Wang
5. Ruijuan Zheng
6. Zhenling Cui
7. Zhonghua Liu
8. Xiangyang Wu
9. Jie Wang
10. Xiaochen Huang
11. Zhaohui Wang
12. Mingqiao Wang
13. Rong Pan
14. Stefan H.E. Kaufmann
15. Xun Meng
16. Lu Zhang
17. Wei Sha
18. Haipeng Liu

• Curated by eLife

  eLife assessment

  The main idea tested in this work is that host galectin-9 inhibits Mycobacterium tuberculosis (Mtb) growth by recognizing the Mtb cell wall component arabinogalactan (AG) and, as a result, disrupting mycobacterial cell wall structure. Moreover, a similar effect is achieved by anti-AG antibodies. While the hypothesis is intriguing and the work has the potential to make a valuable contribution to Mtb therapy, the evidence presented is incomplete and does not explain several critical points including the dose-independent effect of galectin-9 on Mtb growth and how anti-AG antibodies and galectin-9 access the AG layer of intact Mtb.

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Expression of modified FcγRI enables myeloid cells to elicit robust tumor-specific cytotoxicity

1. Yaron Carmi
2. Leen Farhat-Younis
3. Manho Na
4. Amichai Zarfin
5. Nadine Santana-Magal
6. Alon Richter
7. Aseel Khateeb
8. Amit Gutwillig
9. Diana Rasoulouniriana
10. Annette Gleiberman
11. Lir Beck
12. Tamar Giger
13. Avraham Ashkenazi
14. Adi Barzel
15. Peleg Rider

• Curated by eLife

  eLife assessment

  The findings are fundamental for understanding IgM signaling in myeloid cells. The work is compelling in its ability to manipulate and harness myeloid cells to further anti-tumor immunity.

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Amphibian mast cells: barriers to deadly chytrid fungus infections

1. Kelsey A. Hauser
2. Muhammad R. H. Hossainey
3. Lindsey K. Gentry
4. Christina N. Garvey
5. Netra Ranganathan
6. Amulya Yaparla
7. Namarta Kalia
8. Mira Zelle
9. Elizabeth J. Jones
10. Anju N. Duttargi
11. Louise A. Rollins-Smith
12. Carly R. Muletz-Wolz
13. Leon Grayfer

• Curated by eLife

  eLife assessment

  Overall, this is a significant study, and it is able to highlight mast cells in amphibians and their putative capability to respond to and combat fungal infections. Therefore, this study is important for the field. However, the manuscript is incomplete from the standpoint that there is functional data lacking on how these mast cells are activated and their precise functional properties. Such experiments would add substantial impact and rigor and fully support the conclusions.

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Synovial macrophage diversity and activation of M-CSF signaling in post-traumatic osteoarthritis

1. Alexander J. Knights
2. Easton C. Farrell
3. Olivia M. Ellis
4. Michelle J. Song
5. C. Thomas Appleton
6. Tristan Maerz

• Curated by eLife

  eLife assessment

  This study provides useful information by identifying the cell type (macrophages) in synovial tissues involved in the pathogenesis of post-traumatic osteoarthritis (OA) and clarifying distinct transcriptomic signatures that may be a good therapeutic target for OA. However, the analysis performed so far is incomplete, with a main weakness being the lack of data to confirm the authors' speculation about the underlying mechanisms.

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A hepatocyte-specific transcriptional program driven by Rela and Stat3 exacerbates experimental colitis in mice by modulating bile synthesis

1. Jyotsna
2. Binayak Sarkar
3. Mohit Yadav
4. Alvina Deka
5. Manasvini Markandey
6. Priyadarshini Sanyal
7. Perumal Nagarajan
8. Nilesh Gaikward
9. Vineet Ahuja
10. Debasisa Mohanty
11. Soumen Basak
12. Rajesh S Gokhale

• Curated by eLife

  eLife assessment

  This important study reveals the RelA/Stat3-dependent gene program in the liver influences intestinal homeostasis. The evidence supporting the conclusions is compelling, although some additional experiments will strengthen the study. The work will be of interest to scientists in gastrointestinal research fields.

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G protein subunit Gγ13-mediated signaling pathway is critical to the inflammation resolution and functional recovery of severely injured lungs

1. Yi-Hong Li
2. Yi-Sen Yang
3. Yan-Bo Xue
4. Hao Lei
5. Sai-Sai Zhang
6. Junbin Qian
7. Yushi Yao
8. Ruhong Zhou
9. Liquan Huang

• Curated by eLife

  eLife assessment

  This in principle useful study suggests that the G-protein subunit Gng13 is required for limiting injury and inflammation following H1N1 influenza infection via anti-inflammatory effects from ectopic tuft cells. There appears to be support for Gng13 helping to limit influenza injury in the transgenic mouse models used here, but evidence for these effects being mediated by tuft cells is incomplete, giving conflicting data from mice that lack tuft cells entirely.

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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.

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WASP facilitates tumor mechanosensitivity in T lymphocytes

1. Srishti Mandal
2. Mariane Melo
3. Pavlo Gordiichuk
4. Sayanti Acharya
5. Yeh-Chuin Poh
6. Na Li
7. Aereas Aung
8. Eric L. Dane
9. Darrell J. Irvine
10. Sudha Kumari

• Curated by eLife

  eLife assessment

  This valuable study employs a diverse array of techniques encompassing cell biological manipulations, biophysical measurements, and mouse models to elucidate the impact of target cell stiffness on CD8+ cytotoxic T cell activation, with a particular focus on the actin nucleator protein WASP. The finding that WASP is essential for the stiffness-dependent phosphorylation of ZAP70 in CD8 T cells is convincing. However, the data regarding the role of WASP in mechanosensing within CD8 T cell-mediated anti-tumor immunity is incomplete and would benefit from a more rigorous study design. This work would be of interest to cell biologists and investigators studying mechanosensing within the immune system.

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A novel MARV glycoprotein-specific antibody with potentials of broad-spectrum neutralization to filovirus

1. Yuting Zhang
2. Min Zhang
3. Haiyan Wu
4. Xinwei Wang
5. Hang Zheng
6. Junjuan Feng
7. Jing Wang
8. Longlong Luo
9. He Xiao
10. Chunxia Qiao
11. Xinying Li
12. Yuanqiang Zheng
13. Weijin Huang
14. Youchun Wang
15. Yi Wang
16. Yanchun Shi
17. Jiannan Feng
18. Guojiang Chen

• Curated by eLife

  eLife assessment

  In this valuable study, the discovery and subsequent design of the AF03-NL chimeric antibody led to a tool for studying filoviruses and provides a possible blueprint for future therapeutics. In general, the data presented are solid, although further improvements can be made in the overall presentation of the results. The work will be of interest to virologists studying antibodies.

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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.

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MARCO in alveolar macrophages negatively regulates Ace expression and aldosterone production

• Curated by eLife

  eLife assessment

  O'Brien and co-authors addressed how statins reduce levels of aldosterone in humans and provide important data demonstrating that tissue-resident macrophages can exert physiological functions and influence endocrine systems. However, the strength of evidence, as of now, is incomplete, as the sole description of the phenotype of MARCO-deficient mice is insufficient to claim that MARCO in alveolar macrophages can negatively regulate ACE expression and aldosterone production at steady-state. The work will be of broad interest to cell biologists and immunologists.

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Foxp3 depends on Ikaros for control of regulatory T cell gene expression and function

1. Rajan M Thomas
2. Matthew C Pahl
3. Liqing Wang
4. Struan FA Grant
5. Wayne W Hancock
6. Andrew D Wells

• Curated by eLife

  eLife assessment

  This comprehensive study provides valuable information on the cooperation of Ikaros with Foxp3 to establish and regulate a major portion of the epigenome and transcriptome of T-regulatory cells. While the data are compelling, the evidence that these features are solely intrinsic, independent of the micro-environment, could be strengthened.

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Comprehensive analysis of nasal IgA antibodies induced by intranasal administration of the SARS-CoV-2 spike protein

1. Kentarou Waki
2. Hideki Tani
3. Yumiko Saga
4. Takahisa Shimada
5. Emiko Yamazaki
6. Seiichi Koike
7. Okada Mana
8. Masaharu Isobe
9. Nobuyuki Kurosawa

• Curated by eLife

  eLife assessment

  This work provides valuable insights into mucosal antibody responses against SARS-CoV-2 following intranasal immunization by characterizing a large number of monoclonal antibodies at both mucosal and non-mucosal sites. The evidence supporting the claims is overall solid, although the flow cytometric assessment of antibody-expressing cells would benefit from more rigorous controls. The demonstrated in vitro antiviral activity of antibodies characterized provides a rationale for developing mucosal vaccines, especially if confirmed in vivo and benchmarked against antibodies generated following intramuscular vaccination.

Reviewed by eLife

Title to be confirmed

• Curated by eLife

  eLife assessment

  Brodsky and colleagues report here an unexpected cis-activation mechanism of caspase-11. The authors use cellular imaging methods and cleavage site mutants to show that the LPS-induced speck formation by caspase-11 depends on the autoprocessing between two subdomains. This new finding opens multiple doors for further investigating how this non-canonical inflammasome is regulated and activated at the molecular level.

Reviewed by eLife

Transposable elements regulate thymus development and function

1. Jean-David Larouche
2. Céline M Laumont
3. Assya Trofimov
4. Krystel Vincent
5. Leslie Hesnard
6. Sylvie Brochu
7. Caroline Côté
8. Juliette F Humeau
9. Éric Bonneil
10. Joel Lanoix
11. Chantal Durette
12. Patrick Gendron
13. Jean-Philippe Laverdure
14. Ellen R Richie
15. Sébastien Lemieux
16. Pierre Thibault
17. Claude Perreault

• Curated by eLife

  eLife assessment

  This important study shows, based on analyses of single-cell RNA-seq data sets of thymus cells, that transposable elements (TEs) are broadly expressed in thymic stromal cells, especially in medullary thymic epithelial cells and plasamacytoid dendritic cells. The authors also show that at least some TE-derived peptides are presented by MHC-I molecules in the thymus. The study provides solid findings supporting a role of TEs in thymic T-cell selection and immune self-tolerance.

Reviewed by eLife

Transposable elements regulate thymus development and function

1. Jean-David Larouche
2. Céline M Laumont
3. Assya Trofimov
4. Krystel Vincent
5. Leslie Hesnard
6. Sylvie Brochu
7. Caroline Côté
8. Juliette F Humeau
9. Éric Bonneil
10. Joel Lanoix
11. Chantal Durette
12. Patrick Gendron
13. Jean-Philippe Laverdure
14. Ellen R Richie
15. Sébastien Lemieux
16. Pierre Thibault
17. Claude Perreault

• Curated by eLife

  eLife assessment

  This important study shows, based on analyses of single-cell RNA-seq data sets of thymus cells, that transposable elements (TEs) are broadly expressed in thymic stromal cells, especially in medullary thymic epithelial cells and plasamacytoid dendritic cells. The authors also show that at least some TE-derived peptides are presented by MHC-I molecules in the thymus. The study provides solid findings supporting a role of TEs in thymic T-cell selection and immune self-tolerance.

Reviewed by eLife

RAG1 and RAG2 Non-core Regions Are Implicated in Leukemogenesis and Off-target V(D)J Recombination in BCR-ABL1-driven B-cell Lineage Lym-phoblastic Leukemia

1. Xiaozhuo Yu
2. Wen Zhou
3. Xiaodong Chen
4. Shunyu He
5. Mengting Qin
6. Meng Yuan
7. Yang Wang
8. Woodvine otieno Odhiambo
9. Yinsha Miao
10. Yanhong Ji

• Curated by eLife

  eLife assessment

  The authors have shown a valuable tumor suppressive function of the non-core regions of RAG1/2 recombinases, by using a set of animal models. The work is solid and the conclusions are supported by their data. Some areas of mechanistic work can be improved.

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

H2-O deficiency promotes regulatory T cell differentiation and CD4 hyperactivity

• Curated by eLife

  eLife assessment

  This paper seeks to understand how the presentation of peptides by medullary thymic epithelial cells may be regulated by the MHCII peptide loading modulator, H2-O, and how this may affect the selection of regulatory T (Treg) cells. Further work is needed to ensure that the findings are robust: currently the analysis of data is inadequate and inconsistencies in the reported findings are not placed in context with results from other groups. The current version does not provide sufficient support for the claims regarding the effects on Treg cell selection.

Reviewed by eLife

Inhibiting NINJ1-dependent plasma membrane rupture protects against inflammasome-induced blood coagulation and inflammation

1. Jian Cui
2. Hua Li
3. Guoying Zhang
4. Yan Zhang
5. Ling Yang
6. Martha M.S. Sim
7. Jeremy P. Wood
8. Yinan Wei
9. Zhenyu Li
10. Congqing Wu

• Curated by eLife

  eLife assessment

  The authors aim to elucidate the mechanism by which pyroptosis contributes to the increased release of procoagulant tissue factor-containing microvesicles. The data are intriguing and attempt to shed light on the mechanism by which GSDMD plays a role in releasing tissue factor-containing microvesicles, albeit incomplete. The manuscript offers valuable information to unveil new therapeutic targets in human diseases such as sepsis, which can be further strengthened by consulting the reviewers' suggestions.

Reviewed by eLife