bims-inflin 2025-02-09 papers

Nat Commun. 2025 Feb 04. 16(1): 1343

The autophagy component LC3 regulates lymphocyte adhesion via LFA1 transport in response to outside-in signaling.

Naoyuki Kondo, Yuko Mimori-Kiyosue, Keizo Tokuhiro, Giuseppe Pezzotti, Tatsuo Kinashi.

The leukocyte integrin LFA1 is indispensable for immune responses, orchestrating lymphocyte trafficking and adhesion. While LFA1 activation induces LFA1 clustering at the cell contact surface via outside-in signaling, the regulatory mechanisms remain unclear. Here, we uncovered a previously hidden function of the autophagosome component LC3 beyond its role in autophagy by bridging two seemingly unrelated pathways: LFA1 transport and autophagosome transport. LFA1 clusters co-trafficked with LC3, facilitating LFA1 accumulation at the contact surface. LC3b knockout decreased lymphocyte adhesiveness. LFA1 activation did not induce autophagy, whereas it increased mTOR and AMPK activity. LFA1-dependent AMPK activation enhances LFA1 and LC3 clustering and adhesion. Inhibiting Mst1 kinase-mediated LC3 phosphorylation promoted LC3-mediated LFA1 recruitment to the contact surface through direct interaction with RAPL, uncovering an unprecedented integrin recruitment route. These findings uncover a function of LC3 and expand our understanding of lymphocyte regulation via LFA1.

DOI: https://doi.org/10.1038/s41467-025-56631-1

Nat Cardiovasc Res. 2025 Feb 06.

IL-1β enhances susceptibility to atrial fibrillation in mice by acting through resident macrophages and promoting caspase-1 expression.

Oscar Moreno-Loaiza, Vinicius Cardoso Soares, Manuela de Assumpção Souza, Narendra Vera-Nuñez, Ainhoa Rodriguez de Yurre Guirao, Tatiana Pereira da Silva, Ana Beatriz Pozes, Larissa Perticarrari, Evelin Monteiro, Maria Clara Albino, Sophia Barros Silva, Suelen Silva Gomes Dias, Leonardo Maciel, Humberto Muzi-Filho, Dahienne Ferreira de Oliveira, Bruno Cabral Braga, Luan Pereira Diniz, Mario Costa Cruz, Simone Reis Barbosa, Archimedes Barbosa Castro-Junior, Luciana Conde, Mauro Jorge Cabral-Castro, Olga Ferreira de Souza, Martha Valéria Tavares Pinheiro, Nilson Araújo de Oliveira Junior, Leonardo Rezende de Siqueira, Rodrigo Periquito Cosenza, Claudio Munhoz da Fontoura, Jose Carlos Pizzolante Secco, Juliana da Rocha Ferreira, Andréa Silvestre de Sousa, Denilson Albuquerque, Ronir Raggio Luiz, Pedro Nicolau-Neto, Marco Antonio Pretti, Mariana Boroni, Martin Hernán Bonamino, Tais Hanae Kasai-Brunswick, Debora Bastos Mello, Triciana Gonçalves-Silva, Isalira Peroba Ramos, Fernando A Bozza, João Paulo do Vale Madeiro, Roberto Coury Pedrosa, Marcela Sorelli Carneiro-Ramos, Herculano da Silva Martinho, Patrícia T Bozza, Fernanda Mesquita de Souza, Gabriel Victor Lucena da Silva, Thiago M Cunha, Ilija Uzelac, Flavio Fenton, Renata Moll-Bernardes, Claudia N Paiva, Ariel L Escobar, Emiliano Medei.

Atrial fibrillation (AF) is more prevalent in patients with elevated interleukin (IL)-1β levels. Here we show that daily administration of IL-1β for 15 days sensitizes mice to AF, leading to fibrosis, accumulation of β-pleated sheet proteins in the left atrium, and systemic inflammation, resembling the pathophysiological changes observed in patients with AF. IL-1β administration creates a positive feedback loop, dependent on the IL-1 receptor (IL-1R) activity in cardiac resident macrophages. This results in increased caspase-1 maturation in the left atrium and elevated Il1b and Casp1 transcription in atrial macrophages. IL-1β treatment accelerated action potential and Ca2+ restitution in the left atrium, leading to action-potential shortening. This, along with increased caspase-1 maturation and IL-1R signaling, was essential for inducing AF. Lack of IL-1R in macrophages, but not cardiomyocytes, prevented IL-1β-induced AF sensitivity. By depleting recruited macrophages or deleting IL-1R specifically in cardiac resident macrophages, we further demonstrate that IL-1β/IL-1R signaling in these resident macrophages is responsible for increased AF susceptibility. These findings offer insights into the therapeutic potential of targeting IL-1β/IL-1R signaling in patients with AF and emphasize the importance of recognizing different underlying causes in this patient group.

DOI: https://doi.org/10.1038/s44161-025-00610-8

Nat Commun. 2025 Jan 31. 16(1): 1230

A multi-omics spatial framework for host-microbiome dissection within the intestinal tissue microenvironment.

Bokai Zhu, Yunhao Bai, Yao Yu Yeo, Xiaowei Lu, Xavier Rovira-Clavé, Han Chen, Jason Yeung, Dingani Nkosi, Jonathan Glickman, Antonio Delgado-Gonzalez, Georg K Gerber, Mike Angelo, Alex K Shalek, Garry P Nolan, Sizun Jiang.

The intricate interactions between the host immune system and its microbiome constituents undergo dynamic shifts in response to perturbations to the intestinal tissue environment. Our ability to study these events on the systems level is significantly limited by in situ approaches capable of generating simultaneous insights from both host and microbial communities. Here, we introduce Microbiome Cartography (MicroCart), a framework for simultaneous in situ probing of host and microbiome across multiple spatial modalities. We demonstrate MicroCart by investigating gut host and microbiome changes in a murine colitis model, using spatial proteomics, transcriptomics, and glycomics. Our findings reveal a global but systematic transformation in tissue immune responses, encompassing tissue-level remodeling in response to host immune and epithelial cell state perturbations, bacterial population shifts, localized inflammatory responses, and metabolic process alterations during colitis. MicroCart enables a deep investigation of the intricate interplay between the host tissue and its microbiome with spatial multi-omics.

DOI: https://doi.org/10.1038/s41467-025-56237-7