Immunology

HIV-specific CD8+ T-cell responses soon after treatment initiation during acute HIV infection are associated with viral reservoir decline

1. Pien M van Paassen
2. Alexander O Pasternak
3. Karel A van Dort
4. Ad C van Nuenen
5. Irma Maurer
6. Brigitte Boeser-Nunnink
7. Ninée VEJ Buchholtz
8. Tokameh Mahmoudi
9. Cynthia Lungu
10. Reinout van Crevel
11. Casper Rokx
12. Jori Symons
13. Monique Nijhuis
14. Annelou van der Veen
15. Liffert Vogt
16. Michelle J Klouwens
17. Jan M Prins
18. Neeltje A Kootstra
19. Godelieve J de Bree

• Curated by eLife

  eLife Assessment

  The findings of this study are valuable as it demonstrates that when treatment is initiated during acute infection, HIV specific CD8 T cell responses are maintained long term and continued proliferative capacity of these cells may play a role in reducing HIV DNA levels. The evidence supporting the conclusions are solid with rigorous and advanced methodology used with the major limitations being that the findings are association level and do not meet strict criteria for causality. The work is of interest to the HIV cure field and suggests that enhancing early HIV specific CD8 T cell responses should be considered in the design of interventional cure strategies.

Reviewed by eLife

Epigenetic Adaptation Drives Monocyte Differentiation into Microglia-Like Cells Upon Engraftment into the Central Nervous System

1. Jie Liu
2. Fengyang Lei
3. Bin Yan
4. Tian Cao
5. Naiwen Cui
6. Jyoti Sharma
7. Victor Correa
8. Lara Roach
9. Savvas Nicolaou
10. Kristen Pitts
11. James Chodosh
12. Daniel E Maidana
13. Demetrios Vavvas
14. Milica A Margeta
15. Huidan Zhang
16. David Weitz
17. Raul Mostoslavsky
18. Eleftherios I Paschalis

• Curated by eLife

  eLife Assessment

  The authors investigated the epigenetic mechanisms regulating the differentiation of circulating monocytes that infiltrate the CNS and adopt microglia-like characteristics. The work is useful to the field, as the contribution of circulating myeloid cell-derived microglia remains controversial. However, the evidence presented is inadequate as the analyses are based on a very limited set of genes, which does not sufficiently support the authors' central claims.

Reviewed by eLife

Direct contact between iPSC-derived macrophages and hepatocytes drives reciprocal acquisition of Kupffer cell identity and hepatocyte maturation

1. Christopher Zhe Wei Lee
2. Farah Tasnim
3. Xiaozhong Huang
4. Raman Sethi
5. Yoohyun Song
6. Tatsuya Kozaki
7. Sebastiaan De Schepper
8. Nicholas Ang
9. Ivy Low
10. You Yi Hwang
11. Jinmiao Chen
12. Hanry Yu
13. Florent Ginhoux

• Curated by eLife

  eLife Assessment

  This timely and fundamental study introduces a human iPSC-based co-culture system that models Kupffer cell-hepatocyte interactions and aims to recapitulate liver-specific immune-parenchymal dynamics. Direct contact between iMacs and iHeps promotes mutual tissue-specific maturation, with iHeps downregulating fetal genes while iMacs acquire a Kupffer cell-like profile. This convincing in vitro model holds significant promise and is a leap forward; future experimental understanding will enhance its translational impact.

Reviewed by eLife

Contrasting roles for IKK regulated inflammatory signalling pathways for development and maintenance of type 1 and adaptive γδ T cells

1. Farjana Islam
2. Cayman Williams
3. Thea Hogan
4. Louise Webb
5. Ines Boal-Carvalho
6. Benedict Seddon

• Curated by eLife

  eLife Assessment

  This study provides valuable insights into the role of the NF-kB and IKK signaling pathways in γδ T cell development and survival, using robust genetic mouse models. While the research is methodologically sound, some conclusions require further evidence, with incomplete analyses, particularly regarding cell-intrinsic effects and mechanistic details. Overall, the findings are significant for immunologists interested in innate-like T cell biology and advancing the understanding of γδ T cell differentiation and maintenance.

Reviewed by eLife

Ex vivo and in vivo CRISPR/Cas9 screenings identify the roles of protein N-glycosylation in regulating T-cell activation and functions

1. Yu Hong
2. Xiaofang Si
3. Wenjing Liu
4. Xueying Mai
5. Yu Zhang

• Curated by eLife

  eLife Assessment

  This valuable work investigates the role of protein N-glycosylation in regulating T-cell activation and function and suggests that B4GALT1 is a potential target for tumor immunotherapy. The strength of evidence is solid, and further mechanistic validation could be provided.

Reviewed by eLife

HEB collaborates with TCR signaling to upregulate Id3 and enable γδT17 cell maturation in the fetal thymus

1. Johanna S Selvaratnam
2. Juliana Dutra Barbosa da Rocha
3. Vinothkumar Rajan
4. Helen Wang
5. Emily C Reddy
6. Jenny Jiahuan Liu
7. Miki S Gams
8. Cornelis Murre
9. David L Wiest
10. Cynthia J Guidos
11. Juan Carlos Zúñiga-Pflücker
12. Michele K Anderson

• Curated by eLife

  eLife Assessment

  The study provides important mechanistic insight into the transcriptional control of γδT17 development, elegantly demonstrating how HEB and Id3 act sequentially and cooperatively to regulate γδT17 cell specification and maturation. The study provides compelling evidence that advances the understanding of E-Id protein dynamics in thymic T cell specification. The work is comprehensive, technically rigorous, and conceptually clear, and will be of interest to immunologists, developmental biologists, and those studying the molecular underpinnings of physiological outcomes.

Reviewed by eLife

A major histocompatibility complex (MHC) class II molecule that binds the same viral pathogen peptide with both nonamer and decamer core sequences for presentation to T cells

1. Anastasia Goryanin
2. Atlanta G Cook
3. Shahriar Behboudi
4. Jim Kaufman
5. Samer Halabi

Reviewed by preLights

B cell expression of the enzyme PexRAP, an intermediary in ether lipid biosynthesis, promotes antibody responses and germinal center size

1. Sung Hoon Cho
2. Marissa A Jones
3. Kaylor Meyer
4. David M Anderson
5. Sergei Chetyrkin
6. M Wade Calcutt
7. Richard M Caprioli
8. Clay F Semenkovich
9. Mark R Boothby

• Curated by eLife

  eLife Assessment

  This study provides useful insights into the ways in which germinal center B cell metabolism, particularly lipid metabolism, affects cellular responses. The authors use sophisticated mouse models to convincingly demonstrate that ether lipids are relevant for B cell homeostasis and efficient humoral responses. The authors then conducted in vivo as well as in vitro experiments, thereby strengthening their conclusions.

Reviewed by eLife

Explosive cytotoxicity of ‘ruptoblasts’ bridges hormonal surveillance and immune defense

1. Chew Chai
2. Eliya Sultan
3. Souradeep R. Sarkar
4. Lihan Zhong
5. Dania Nanes Sarfati
6. Orly Gershoni-Yahalom
7. Christine Jacobs-Wagner
8. Hawa Racine Thiam
9. Benyamin Rosental
10. Bo Wang

Reviewed by preLights

RadD from Fusobacterium nucleatum Engages NKp46 to Promote Antitumor Cytotoxicity

1. Ahmed Rishiq
2. Johanna Galski
3. Reem Bsoul
4. Mingdong Liu
5. Rema Darawshe
6. Renate Lux
7. Gilad Bachrach
8. Ofer Mandelboim

• Curated by eLife

  eLife Assessment

  This useful study describes a mechanism of microbial modulation of anti-tumor immunity, which is of considerable interest in the field. However, the experimental supports for the key mechanistic claim, the interaction between RadD and NKp46, are not robust. Multiple experimental inconsistencies, especially in vivo, weaken the conclusions, making the strength of evidence incomplete. Additional controls, direct binding assays, and clarification of in vivo mechanistic relevance would strengthen the work.

Reviewed by eLife