Immunology

TLR2 regulates hair follicle cycle and regeneration via BMP signaling

1. Luyang Xiong
2. Irina Zhevlakova
3. Xiaoxia Z West
4. Detao Gao
5. Rakhilya Murtazina
6. Anthony Horak
7. J Mark Brown
8. Iuliia Molokotina
9. Eugene A Podrez
10. Tatiana V Byzova

• Curated by eLife

  eLife assessment

  Toll like receptor 2 (TLR2) signaling has traditionally been viewed a surface protein that induces innate immune responses and improves acquired immunity. Here, the authors suggest a different role for TLR2 in the hair cycle. By using a Cre reporter that is largely, but not solely active in hair follicle stem cells, the authors conditionally delete Tlr2 in mice and report that BMP signaling is sustained and hair cycle entry is delayed. Delving further, the authors identify CEP (2-ω-carboxyethyl pyrrole) as an endogenous ligand of TLR2 in hair follicle stem cell regulation. Although a role for TLR2 signaling in hair follicle stem cells is potentially novel and important, the reviewers remain in consensus that evidence presented in two significant areas continues to be incomplete: 1) where TLR2 and CEP are expressed and how specific is their expression to the hair follicle stem cells; 2) whether as the authors suggest, TLR2 functions by regulating BMP signaling in the stem cell niche of the hair follicle.

Reviewed by eLife, preLights

Activation of the P2RX7/IL-18 pathway in immune cells attenuates lung fibrosis

1. Serena Janho dit Hreich
2. Thierry Juhel
3. Sylvie Leroy
4. Alina Ghinet
5. Frederic Brau
6. Veronique Hofman
7. Paul Hofman
8. Valerie Vouret-Craviari

• Curated by eLife

  eLife assessment

  This study presents a potentially valuable discovery which indicates that activation of the P2RX7 pathway by the small molecule HEI3090 can reduce lung fibrosis after its establishment by inflammatory damage. If confirmed, the study could clarify the role of specific immune networks in the establishment and progression of lung fibrosis. The presented data and analyses showing the efficacy of HEI3090 small molecule acting via the P2RX7 pathway in reducing lung fibrosis are solid. The studies also show that genetic deletion of P2RX7 itself can reduce the extent of fibrosis. P2RX7 can thus have distinct effects in various phases of the development of lung fibrosis. There is a need for additional definitive studies that specifically identify the discrete phases of when inflammasome activation via P2RX7 signaling can worsen fibrosis versus when the same signaling can be beneficial. It also needs to be established whether distinct immune cell populations mediate the detrimental and beneficial effects of P2RX7 activation in lung fibrosis.

Reviewed by eLife

Dynamics of macrophage polarization support Salmonella persistence in a whole living organism

1. Jade Leiba
2. Tamara Sipka
3. Christina Begon-Pescia
4. Matteo Bernardello
5. Sofiane Tairi
6. Lionello Bossi
7. Anne-Alicia Gonzalez
8. Xavier Mialhe
9. Emilio J Gualda
10. Pablo Loza-Alvarez
11. Anne Blanc-Potard
12. Georges Lutfalla
13. Mai E Nguyen-Chi

• Curated by eLife

  eLife assessment

  This useful study introduces the development of Salmonella infection model in zebrafish embryos as an important model to study the interaction between macrophages and Salmonella during in vivo infection. Overall, the data presented are convincing and provide an inventory of genes mediating macrophage cell-cell adhesion and interactions that are useful for dissecting tissue macrophage responses and heterogeneity during intracellular bacterial infection. This is important to characterize the infection outcome and the dynamics of the immune response. The work will be of interest to microbiologists.

Reviewed by eLife

Disease-associated astrocyte epigenetic memory promotes CNS pathology

1. Hong-Gyun Lee
2. Joseph M. Rone
3. Zhaorong Li
4. Camilo Faust Akl
5. Seung Won Shin
6. Joon-Hyuk Lee
7. Lucas E. Flausino
8. Florian Pernin
9. Chun-Cheih Chao
10. Kilian L. Kleemann
11. Lena Srun
12. Tomer Illouz
13. Federico Giovannoni
14. Marc Charabati
15. Liliana M. Sanmarco
16. Jessica E. Kenison
17. Gavin Piester
18. Stephanie E. J. Zandee
19. Jack P. Antel
20. Veit Rothhammer
21. Michael A. Wheeler
22. Alexandre Prat
23. Iain C. Clark
24. Francisco J. Quintana

Reviewed by Arcadia Science

β-Carotene accelerates the resolution of atherosclerosis in mice

1. Ivan Pinos
2. Johana Coronel
3. Asma'a Albakri
4. Amparo Blanco
5. Patrick McQueen
6. Donald Molina
7. JaeYoung Sim
8. Edward A Fisher
9. Jaume Amengual

• Curated by eLife

  eLife assessment

  This study presents an important conceptual advance of how vitamin A and its derivatives contribute to atherosclerosis. There is solid evidence for the contributions of specialized populations of T cells in atherosclerosis resolution, including use of multiple in vivo models to validate the functional effects. A limitation is the insufficient analysis of lesions, but the manuscript has been improved from the original preprint version and the overarching conclusions have been refined.

Reviewed by eLife

Tailoring Tfh profiles enhances antibody persistence to a clade C HIV-1 vaccine in rhesus macaques

1. Anil Verma
2. Chase E Hawes
3. Sonny R Elizaldi
4. Justin C Smith
5. Dhivyaa Rajasundaram
6. Gabriel Kristian Pedersen
7. Xiaoying Shen
8. LaTonya D Williams
9. Georgia D Tomaras
10. Pamela A Kozlowski
11. Rama R Amara
12. Smita S Iyer

• Curated by eLife

  eLife assessment

  The authors' findings have theoretical or practical deep implications, which makes them important. The methods, data, and analyzes support the authors' arguments with only minor weaknesses, and overall they are solid. In vitro culture experiments could provide evidence to strengthen the evidence for the functional significance of Th1-mediated cytokines in the observed B cell responses.

Reviewed by eLife

Novel Association of Lyme disease, Age, and Atopic Dermatitis

1. Brandon T. Lee
2. Sarah D. Galloway
3. Qingying Feng
4. Satu Strausz
5. Maia Shoham
6. Paige Hansen
7. Laughing Bear Torrez Dulgeroff
8. Grace Blacker
9. Ying Y. Yiu
10. Paul Mansfield
11. FinnGen
12. Atif Saleem
13. Eric Gars
14. Erin C. Sanders
15. Irving L. Weissman
16. Hanna M. Ollila
17. Michal Caspi Tal

Reviewed by Arcadia Science

Piezo1 mechanosensing regulates integrin-dependent chemotactic migration in human T cells

1. Chinky Shiu Chen Liu
2. Tithi Mandal
3. Parijat Biswas
4. Md Asmaul Hoque
5. Purbita Bandopadhyay
6. Bishnu Prasad Sinha
7. Jafar Sarif
8. Ranit D'Rozario
9. Deepak Kumar Sinha
10. Bidisha Sinha
11. Dipyaman Ganguly

• Curated by eLife

  eLife assessment

  This study provides useful insights into the subcellular localization, interaction with integrins, and functional importance of the cell surface receptor Piezo1 in migrating human T-cells. Whether Piezo1 is critically sensing mechano-physical cues during T-cell migration is however not well supported by direct experimental evidence. The data collected is solid otherwise.

Reviewed by eLife

NAD+ prevents septic shock-induced death by non-canonical inflammasome blockade and IL-10 cytokine production in macrophages

1. Jasper Iske
2. Rachid El Fatimy
3. Yeqi Nian
4. Amina Ghouzlani
5. Siawosh K Eskandari
6. Hector Rodriguez Cetina Biefer
7. Anju Vasudevan
8. Abdallah Elkhal

• Curated by eLife

  eLife assessment

  In this valuable contribution, the authors demonstrate that the infusion of NAD+ may prevent death and reduce disease severity from lethal experimental bacterial sepsis, possibly through inflammasome inhibition, without reducing bacterial load. They provide solid evidence for these protective effects of NAD+, though the precise mechanisms involved remain unclear and need further support and elucidation. The core findings may well have clinical implications but, in addition to mechanistic clarifications, contextualised interpretation as metabolic adaptation to sepsis would create wider interest.

Reviewed by eLife

Ym1 protein crystals promote type 2 immunity

1. Ines Heyndrickx
2. Kim Deswarte
3. Kenneth Verstraete
4. Koen HG Verschueren
5. Ursula Smole
6. Helena Aegerter
7. Ann Dansercoer
8. Hamida Hammad
9. Savvas N Savvides
10. Bart N Lambrecht

• Curated by eLife

  eLife assessment

  This is an important and interesting account of the ability of Ym1 crystals to promote type 2 immunity in vivo, in mice. The data presented are compelling, building on and significantly advancing evidence this group has previously published on the type 2 immunogenicity of other protein crystals. The work will be of relevant interest to immunologists and researchers working on type 2 inflammatory disease, in the lung and in others tissues.

Reviewed by eLife