Immunology

Apoptotic signaling clears engineered Salmonella in an organ-specific manner

1. Taylor J Abele
2. Zachary P Billman
3. Lupeng Li
4. Carissa K Harvest
5. Alexia K Bryan
6. Gabrielle R Magalski
7. Joseph P Lopez
8. Heather N Larson
9. Xiao-Ming Yin
10. Edward A Miao

• Curated by eLife

  eLife assessment

  Host cell death is an effective strategy to protect against infection, and is believed to function primarily by the elimination of the intracellular niche for pathogen replication. Abele and colleagues address an important question: does the mode of cell death affect its effectiveness in pathogen clearance? Consistent with prior observations, the authors provide compelling new evidence that the answer can depend on the cell type and/or tissue involved.

Reviewed by eLife

CTLA-4 antibody-drug conjugate reveals autologous destruction of B-lymphocytes associated with regulatory T cell impairment

1. Musleh M Muthana
2. Xuexiang Du
3. Mingyue Liu
4. Xu Wang
5. Wei Wu
6. Chunxia Ai
7. Lishan Su
8. Pan Zheng
9. Yang Liu

• Curated by eLife

  eLife assessment

  This valuable study presents presents solid evidence that an anti-CTLA-4 antibody drug conjugate transiently depletes circulating B cells in a mouse model, showing how dysregulation of the T cell immune system can impact B cell homeostasis. The work will be of broad interest to immunologists and medical biologists, but a major limitation is that the mechanism of B-cell reduction remains unclear, as evidence of killing of B-cells by T-cells is not presented.

Reviewed by eLife

Regulation of pDC fate determination by histone deacetylase 3

1. Yijun Zhang
2. Tao Wu
3. Zhimin He
4. Wenlong Lai
5. Xiangyi Shen
6. Jiaoyan Lv
7. Yuanhao Wang
8. Li Wu

• Curated by eLife

  eLife assessment

  This study examines the expression of HDAC3 within DC compartment. Taking advantage of tamoxifen inducible ERT2-cre mouse model they observe the dependency of pDCs but not cDCs on HDAC3. The requirement of this histone modifier appears to occur during development around the CLP stage. Tamoxifen treated mice lack almost all pDC besides lymphoid progenitors. RNA seq studies identify multiple DC specific target genes within the remaining pDC - using Cut and Tag technology they validate some of the identified targets of HDAC3. Taken together, this study shows the requirement of HDAC3 on pDC but not cDC, congruent with the recent findings of a lymphoid origin of pDC.

Reviewed by eLife

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

1. Robin A. Welsh
2. Nianbin Song
3. Chan-Su Park
4. J. David Peske
5. Scheherazade Sadegh-Nasseri

• 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

De novo fatty-acid synthesis protects invariant NKT cells from cell death, thereby promoting their homeostasis and pathogenic roles in airway hyperresponsiveness

1. Jaemoon Koh
2. Yeon Duk Woo
3. Hyun Jung Yoo
4. Jun-Pyo Choi
5. Sae Hoon Kim
6. Yoon-Seok Chang
7. Kyeong Cheon Jung
8. Ji Hyung Kim
9. Yoon Kyung Jeon
10. Hye Young Kim
11. Doo Hyun Chung

• Curated by eLife

  eLife assessment

  The study's results offer a fundamental insight into how ACC1-mediated fatty-acid synthesis affects the survival and pathogenicity of iNKT cells in allergic asthma. The inclusion of mouse models, involving genetic adjustments and reconstitution experiments, along with the disparities found in iNKT cells between allergic asthma patients and control subjects in human studies, adds compelling evidence that substantiates these findings.

Reviewed by eLife

NAD+ metabolism is a key modulator of bacterial respiratory epithelial infections

1. Björn Klabunde
2. André Wesener
3. Wilhelm Bertrams
4. Isabell Beinborn
5. Nicole Paczia
6. Kristin Surmann
7. Sascha Blankenburg
8. Jochen Wilhelm
9. Javier Serrania
10. Kèvin Knoops
11. Eslam M. Elsayed
12. Katrin Laakmann
13. Anna Lena Jung
14. Andreas Kirschbaum
15. Sven Hammerschmidt
16. Belal Alshaar
17. Nicolas Gisch
18. Mobarak Abu Mraheil
19. Anke Becker
20. Uwe Völker
21. Evelyn Vollmeister
22. Birke J. Benedikter
23. Bernd Schmeck

Reviewed by preLights

Nanograms of SARS-CoV-2 spike protein delivered by exosomes induce potent neutralization of both delta and omicron variants

1. Mafalda Cacciottolo
2. Yujia Li
3. Justin B. Nice
4. Michael J. LeClaire
5. Ryan Twaddle
6. Ciana L. Mora
7. Stephanie Y. Adachi
8. Meredith Young
9. Jenna Angeles
10. Kristi Elliott
11. Minghao Sun

Reviewed by PREreview

The lncRNA Malat1 inhibits miR-15/16 to enhance cytotoxic T cell activation and memory cell formation

1. Benjamin D Wheeler
2. John D Gagnon
3. Wandi S Zhu
4. Priscila Muñoz-Sandoval
5. Simon K Wong
6. Dimitre S Simeonov
7. Zhongmei Li
8. Rachel DeBarge
9. Matthew H Spitzer
10. Alexander Marson
11. K Mark Ansel

• Curated by eLife

  eLife assessment

  This is an important study that revealed a new noncoding RNA regulatory circuit involved in T cell function. The authors provide compelling evidence, that is more rigorous than the state-of-the-art, using genetically engineered mice and cell-based experiments. The interpretation of the results should be tempered due to the small effect size observed.

Reviewed by eLife

CCR1 mediates Müller cell activation and photoreceptor cell death in macular and retinal degeneration

1. Sarah Elbaz-Hayoun
2. Batya Rinsky
3. Shira Hagbi-Levi
4. Michelle Grunin
5. Itay Chowers

• Curated by eLife

  eLife assessment

  Elbaz-Hayoun et al. investigate the role of macrophages in the gliotic response of retinal Müller glia and photoreceptor cell death. The authors find that macrophages play a role in inducing retinal damage. A role for the muller glia expressed, C-C chemokine receptor axis was identified as a causative factor in promoting retinal degeneration. These important data identify a new link between cells of the immune system and those within the retina which contribute to the progression of retinal degeneration.

Reviewed by eLife

Vaccination with mycobacterial lipid loaded nanoparticle leads to lipid antigen persistence and memory differentiation of antigen-specific T cells

1. Eva Morgun
2. Jennifer Zhu
3. Sultan Almunif
4. Sharan Bobbala
5. Melissa S Aguilar
6. Junzhong Wang
7. Kathleen Conner
8. Yongyong Cui
9. Liang Cao
10. Chetan Seshadri
11. Evan A Scott
12. Chyung-Ru Wang

• Curated by eLife

  eLife assessment

  The authors generate a new formulation built upon a previous nanoparticle platform to generate a new system termed bicontinuous nanospheres (BCN), allowing for the dual incorporation of lipid and protein antigens. The authors generate mycolic acid (MA)-loaded BCN and perform a series of characterization studies to demonstrate the superior performance of this new formulation relative to the original one in terms of antigen persistence, a quality needed to sustain responses after vaccination. This work provides important new insights relevant to the TB vaccine field and it suggests that alternative antigens to proteins could be used in TB vaccine formulations. The data are convincing and will be of interest to individuals working on tuberculosis, vaccines and basic immunology.

Reviewed by eLife