Immunology

PTPN22 R620W gene editing in T cells enhances low-avidity TCR responses

1. Warren Anderson
2. Fariba Barahmand-pour-Whitman
3. Peter S Linsley
4. Karen Cerosaletti
5. Jane H Buckner
6. David J Rawlings

• Curated by eLife

  Evaluation Summary:

  PTPN22 is a protein tyrosine phosphatase which negatively regulates antigen receptor signaling. It has been proposed that several genetic variants of PTPN22 might be loss of function (LOF) variants, leading to hyper-responsive T cell proliferative and effector responses. The authors investigate how the PTPN22 R620W variant, associated with multiple autoimmune diseases, might contribute to breech of peripheral T cell tolerance. This work greatly advances and clarifies ongoing confusion of whether PTPN22 SNP(620W) is a LOF mutant.

  (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

Neutrophil-mediated fibroblast-tumor cell il-6/stat-3 signaling underlies the association between neutrophil-to-lymphocyte ratio dynamics and chemotherapy response in localized pancreatic cancer: A hybrid clinical-preclinical study

1. Iago de Castro Silva
2. Anna Bianchi
3. Nilesh U Deshpande
4. Prateek Sharma
5. Siddharth Mehra
6. Vanessa Tonin Garrido
7. Shannon Jacqueline Saigh
8. Jonathan England
9. Peter Joel Hosein
10. Deukwoo Kwon
11. Nipun B Merchant
12. Jashodeep Datta

• Curated by eLife

  Evaluation Summary:

  Iago De Castro et al, constitute an exciting study conveying to readers that neutrophil-to-lymphocyte ratio dynamics predict pancreatic cancer pathologic response to neoadjuvant therapy. Specifically, the authors aim to determine the effect of gemcitabine/paclitaxel and anti-Ly6G treatment on stromal T cells and CAF populations. They conclude that neutrophil-to-lymphocyte ratios are associated with survival following this treatment and use animal models to show metastatic effects allied to it. The authors attempt to convey that microenvironmental neutrophils could play a causal role in pancreatic cancer chemoresistance. It was agreed that while the discoveries are very interesting, the public could benefit from the authors improving: the relevance to the human condition, providing a stronger link to fibroblastic cell functional transitions, broadening the discussion regarding previous/related published studies, and strengthening the anti-Ly6G specificity proof within the provided data.

  (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

Maternal obesity blunts antimicrobial responses in fetal monocytes

1. Suhas Sureshchandra
2. Brianna M Doratt
3. Norma Mendza
4. Oleg Varlamov
5. Monica Rincon
6. Nicole E Marshall
7. Ilhem Messaoudi

• Curated by eLife

  eLife assessment

  This is an important manuscript that will be of interest to a broad range of researchers studying immunology, obesity and metabolism, as well as the links between maternal health and pathophysiological responses in the offspring. The comprehensive studies using RNA-seq, scRNA-seq, ATAC-seq and scATAC-seq in human umbilical cord monocytes represent an important resource for understanding the transcriptomic and epigenetic shifts in the monocytes of newborns. The experiments involving stimulation of monocytes with pathogens offer convincing evidence for the dysfunction of monocytes in the newborn.

Reviewed by eLife

Meningeal lymphatic drainage promotes T cell responses against Toxoplasma gondii but is dispensable for parasite control in the brain

1. Michael A Kovacs
2. Maureen N Cowan
3. Isaac W Babcock
4. Lydia A Sibley
5. Katherine Still
6. Samantha J Batista
7. Sydney A Labuzan
8. Ish Sethi
9. Tajie H Harris

• Curated by eLife

  Evaluation Summary:

  This manuscript tackles the timely and interesting research question of whether meningeal lymphatic drainage is required for the control of brain infection with Toxoplasma gondii. It contains a sophisticated experimental approach using cutting-edge methods, it has an easy-to-follow narrative, and comes up with an interesting albeit negative finding which the authors even tried to explain by an additional set of experiments. Although there are some limitations and weaknesses of the paper in its present form it will certainly contribute to the growing body of literature on how the once "immune-privileged" CNS is protected against environmental challenges.

  (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.)

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Memory persistence and differentiation into antibody-secreting cells accompanied by positive selection in longitudinal BCR repertoires

1. Artem Mikelov
2. Evgeniia I Alekseeva
3. Ekaterina A Komech
4. Dmitry B Staroverov
5. Maria A Turchaninova
6. Mikhail Shugay
7. Dmitriy M Chudakov
8. Georgii A Bazykin
9. Ivan V Zvyagin

• Curated by eLife

  Evaluation Summary:

  By performing homeostatic longitudinal IgH repertoire analysis of human memory B cells and plasma cells, authors draw two major unique conclusions; first, a high degree of clonal persistence in individual memory B cell subsets with inter individual convergence in memory B and plasma cells; second, reactivation of persisting memory B cells with new rounds of affinity maturation during proliferation and differentiation into plasma cells. These conclusions provide a significant insight into how human memory B and plasma cells are generated in a homeostatic condition.

  (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 structure-selective endonucleases GEN1 and MUS81 mediate complementary functions in safeguarding the genome of proliferating B lymphocytes

1. Keith Conrad Fernandez
2. Laura Feeney
3. Ryan M Smolkin
4. Wei-Feng Yen
5. Allysia J Matthews
6. William Alread
7. John HJ Petrini
8. Jayanta Chaudhuri

• Curated by eLife

  Evaluation Summary:

  This manuscript is of interest to individuals working on genome stability and B lymphocyte development. Using knockouts for the genes encoding the structure-selective endonucleases GEN1 and MUS81 in mice, the authors show that the absence of both proteins is incompatible with embryonic development, with selective loss in mature B-cells inhibiting germinal center formation. This is the first study of these enzymes in an organismic context and in primary cells, revealing insight into the in vivo consequences of loss of MUS81 and GEN1 functions not previously accessible through studies in cultured 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 #1 agreed to share their name with the authors.)

Reviewed by eLife

Role of Rab5 early endosomes in regulating Drosophila gut antibacterial response

1. Manish Joshi
2. Annelise Viallat-Lieutaud
3. Julien Royet

Reviewed by Review Commons

Innate immune signaling in trophoblast and decidua organoids defines differential antiviral defenses at the maternal-fetal interface

1. Liheng Yang
2. Eleanor C Semmes
3. Cristian Ovies
4. Christina Megli
5. Sallie Permar
6. Jennifer B Gilner
7. Carolyn B Coyne

• Curated by eLife

  Evaluation Summary:

  Yang et al. provide a scientifically sound and compelling manuscript characterizing mid-to-late gestation trophoblast and decidual organoids as ex vivo models to study vertically transmitted microbial infections, using human cytomegalovirus as a model pathogen. They demonstrate organoids have tissue-specific immunological responses and susceptibilities to viral infection.

  (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

Single-cell RNA sequencing analysis of shrimp immune cells identifies macrophage-like phagocytes

1. Peng Yang
2. Yaohui Chen
3. Zhiqi Huang
4. Huidan Xia
5. Ling Cheng
6. Hao Wu
7. Yueling Zhang
8. Fan Wang

• Curated by eLife

  Evaluation Summary:

  The shrimp market is growing globally, with 8.12 tons produced in 2020. The market size is thought to reach $55 billion by 2027. Most of the market comes from farms, the white shrimp, Penaeus vannamei, being one of the most commonly farmed species worldwide. The present study provides a single cell transcriptional atlas of the white shrimp, P. vannamei, immune cells in the hemolymph, known as hemocytes. White shrimp single cell RNA sequencing studies uncovered two macrophage-like populations, one of them with markers similar to mammalian macrophages. These findings redefine the current classification of shrimp immune cells which has been done using morphological approaches and via targeted qPCR studies but never using single cell transcriptomics.

  (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

A selective LIS1 requirement for mitotic spindle assembly discriminates distinct T-cell division mechanisms within the T-cell lineage

1. Jérémy Argenty
2. Nelly Rouquié
3. Cyrielle Bories
4. Suzanne Mélique
5. Valérie Duplan-Eche
6. Abdelhadi Saoudi
7. Nicolas Fazilleau
8. Renaud Lesourne

• Curated by eLife

  Evaluation Summary:

  The authors study the requirement for Lis1, a dynein binding protein, in T cells, and present solid evidence that the requirement differs between different T cell lineages, suggesting cell division mechanisms differ across these cell lineages. This work is valuable for cell biologists and immunologists interested in mechanisms that contribute to cell proliferation and differentiation.

  (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