Immunology

Nociceptor Neurons Control Pollution-Mediated Neutrophilic Asthma

1. Jo-Chiao Wang
2. Amelia Kulle
3. Theo Crosson
4. Amin Reza Nikpoor
5. Surbhi Gupta
6. Anais Roger
7. Moutih Rafei
8. Ajitha Thanabalasuriar
9. Sebastien Talbot

• Curated by eLife

  eLife Assessment

  This important work shows that fine particulate matter exposure to the lungs led to nociceptor-dependent neutrophilic inflammation. Likely macrophage-neuronal crosstalk, via release of artemin from macrophages and activation of Gfra3 on the JNC neuron, potentiated the response. The data convincingly strengthens links between pollutants, immune and neural interactions.

Reviewed by eLife

Interleukin 10 controls the balance between tolerance, pathogen elimination, and immunopathology in birds

1. Dominique Meunier
2. Ricardo Corona-Torres
3. Kay Boulton
4. Zhiguang Wu
5. Maeve Ballantyne
6. Laura Glendinning
7. Anum Ali Ahmad
8. Dominika Borowska
9. Lorna Taylor
10. Lonneke Vervelde
11. Jorge del Pozo
12. Marili Vasilogianni
13. José Jaramillo-Ortiz
14. Gonzalo Sanchez-Arsuaga
15. Androniki Psifidi
16. Fiona Tomley
17. Kellie A Watson
18. Michael J McGrew
19. Mark P Stevens
20. Damer P Blake
21. David A Hume

• Curated by eLife

  eLife Assessment

  IL-10 balances protective and deleterious immune functions in mice and humans, but if IL-10 also controls avian intestinal homeostasis remains unclear. Generating genetic knockouts, Meunier et al. established that a complete lack of IL-10 strengthened immunity against enteric bacteria in chickens, while also aggravating infection-inflicted inflammatory tissue damage and dysbiosis upon parasite infection, but unlike mouse models, IL-10 deficiency did not provoke spontaneous colitis in chickens. The findings presented are valuable, and the strength of evidence is convincing. The observation may have implications for the livestock industry and additional studies involving genetic knockouts may further unravel conserved and distinct avian IL-10 controls.

Reviewed by eLife

Beta-Glucan Modulates Monocyte Plasticity and Differentiation Capacity to Mitigate DSS-Induced Colitis

1. Yinyin Lv
2. Yanyun Fan
3. Qingxiang Gao
4. Qiongyun Chen
5. Yiqun Hu
6. Lin Wang
7. Huaxiu Shi
8. Ermei Chen
9. Qinyu Xu
10. Ying Cai
11. Qingqi Fan
12. Linying Li
13. Dan Du
14. Jianlin Ren
15. Shih-Chin Cheng
16. Hongzhi Xu

• Curated by eLife

  eLife Assessment

  This study presents valuable and compelling evidence that β-glucan-induced trained immunity can protect against intestinal inflammation by reprogramming innate immune cells toward a reparative phenotype. The authors employ a convincing combination of functional assays, adoptive transfers, and single-cell transcriptomics to uncover mechanistic insights and demonstrate the therapeutic potential of innate immune memory in IBD. While the work is robust, addressing the underlying epigenetic mechanisms and including additional controls would further reinforce the trained immunity-specific interpretation.

Reviewed by eLife

DGKα and ζ Deficiency Causes Regulatory T-Cell Dysregulation, Destabilization, and Conversion to Pathogenic T-Follicular Helper Cells to Trigger IgG1-Predominant Autoimmunity

1. Lei Li
2. Hongxiang Huang
3. Hongxia Wang
4. Yun Pan
5. Huishan Tao
6. Shimeng Zhang
7. Peer WF Karmaus
8. Michael B Fessler
9. John W Sleasman
10. Xiao-Ping Zhong

• Curated by eLife

  eLife Assessment

  This study presents an important finding on the signaling mechanisms underlying Treg cell homeostasis by identifying the simultaneous requirement of diacylglycerol (DAG) kinases (DGK) alpha and zeta for Foxp3+ Treg cell function and follicular responses, with implications for the pathogenesis of some autoimmune diseases. Whereas data based on the characterization of double knock-out mice (for DGK alpha and zeta) is solid, showing the emergence of autoimmune manifestations, the study has gaps in its experimental approaches since it is not clear what can be attributed to the simultaneous DKGα and ζ deficiency, versus the individual deficiency of either one. Experiments on the pathogenic potential of the DKO Tregs in the absence of other T-cells were not presented and results on the role of CD25 downregulation and CD28-independent activation of Treg cells were not properly discussed. Nonetheless, the reported data would be of interest to immunologists working on T-cell intracellular signaling and autoimmunity.

Reviewed by eLife

Xcr1+ type 1 conventional dendritic cells are essential mediators for atherosclerosis progression

1. Tianhan Li
2. Liaoxun Lu
3. Juanjuan Qiu
4. Xin Dong
5. Le Yang
6. Kexin He
7. Yanrong Gu
8. Binhui Zhou
9. Tingting Jia
10. Toby Lawrence
11. Marie Malissen
12. Guixue Wang
13. Rong Huang
14. Hui Wang
15. Bernard Malissen
16. Yinming Liang
17. Lichen Zhang

• Curated by eLife

  eLife Assessment

  This manuscript by Li, Lu et al., presents important findings on the role of cDC1 in atherosclerosis and their influence on the adaptive immune system. Using Xcr1Cre-Gfp Rosa26LSL-DTA ApoE-/- mouse models, these data convincingly reveal an unexpected, non-redundant role of the XCL1-XCR1 axis in mediating cDC1 contributions to atherosclerosis.

Reviewed by eLife

Synthetic auxotrophy reveals metabolic regulation of plasma cell generation, affinity maturation, and cytokine receptor signaling

1. Sung Hoon Cho
2. Shawna K Brookens
3. Ariel L Raybuck
4. Kaylor Meyer
5. Yeeun C Paik
6. Jennie Hamilton
7. Jingxin Li
8. Karel Kalecky
9. Chloe Park
10. Sakeenah L Hicks
11. John Karijolich
12. Teodoro H Bottiglieri
13. Jeffrey C Rathmell
14. Denis Mogilenko
15. Chris D Scharer
16. Mark R Boothby

• Curated by eLife

  eLife Assessment

  The authors addressed an important biological question, namely the role of glutamine metabolism in humoral responses, and they obtained solid conclusions. The strength of this study is that the authors used state-of-the-art transgenic mouse models together with in vitro analysis, thereby providing significant insights into the question posed. The following would strengthen the manuscript: i) adding more in-depth functionality/physiological relevance in the discussion part, and ii) regarding the experiments, the inclusion of more appropriate controls and a clearer and more accurate description of the methods.

Reviewed by eLife

Tumor-infiltrating CD27 ^- IgD ^- regulatory B cells suppress cytotoxic CD8 ⁺ T cell responses in renal cell carcinoma

1. Zara Baig
2. Isabella Withnell
3. Joseph C.F. Ng
4. Christopher J.M. Piper
5. Hannah F. Bradford
6. Antonio Rullan
7. Edward H. Arbe-Barnes
8. Camila G.X. de Brito
9. Alessandro Di Tullio
10. Thomas J. Mitchell
11. Hans J. Stauss
12. Maxine G.B. Tran
13. Franca Fraternali
14. Claudia Mauri

Reviewed by preLights

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 not 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

Aurora kinase A promotes trained immunity via regulation of endogenous S-adenosylmethionine metabolism

1. Mengyun Li
2. Huan Jin
3. Yongxiang Liu
4. Zining Wang
5. Lin Li
6. Tiantian Wang
7. Xiaojuan Wang
8. Hongxia Zhang
9. Bitao Huo
10. Tiantian Yu
11. Shoujie Wang
12. Wei Zhao
13. Jinyun Liu
14. Peng Huang
15. Jun Cui
16. Xiaojun Xia

• Curated by eLife

  eLife Assessment

  The authors use a range of techniques to examine the role of Aurora Kinase A (AurA) in trained immunity. The study is hypothesis driven, it uses solid experimental approaches, and the data are presented in a logical manner. The findings are valuable to the trained immunity field because they provide an in-depth look at a common inducer of trained immunity, beta-glucan.

Reviewed by eLife

Newly discovered and conserved role of IgM against viral infection in an early vertebrate

1. Weiguang Kong
2. Xinyou Wang
3. Guangyi Ding
4. Peng Yang
5. Yong Shi
6. Chang Cai
7. Xinyi Yang
8. Gaofeng Cheng
9. Fumio Takizawa
10. Zhen Xu

• Curated by eLife

  eLife Assessment

  The manuscript is an important study which aims to demonstrate the conserved and crucial role of IgM in both systemic and mucosal antiviral immunity in teleost, challenging the established differential roles of IgT and IgM. The strength of the evidence is solid and supported by a combination of in vivo studies, viral infection models, and complementary in vitro assays. In the current version, authors validate the MoAb against IgM

Reviewed by eLife