Immunity from non-immune cells

IP: Joan Manils Pacheco, PhD

The human body reacts to dangers such pathogenic microorganisms or tissue damage with a physiological response called inflammation. While inflammation is critical for regeneration and homeostasis, it is also a common driver of pathologies such as autoimmunity and cancer when malfunctioning. Virtually each one of the cells composing the body can kickstart inflammation, and this is largely due to the presence of the transcription factor NF-KB in all of them.

Keratinocytes are active players of the innate immune system; they express a wide variety of receptors to sense pathogens and damage and release proinflammatory cytokines in response to insults. Keratinocytes have their own and unique way to activate NF-KB through CARD14 protein. CARD14 acts as an assembly point for adaptors creating a node that promotes signals within the cell leading to inflammation and skin diseases such psoriasis when mutated. We aim to gain insights into CARD14 fundamental biology, using animal models and molecular approaches to understand and manipulate its activity to fight psoriasis.

Joan Manils' Publons profile

https://orcid.org/0000-0001-8429-1295

PID2021-126249OA-I00. Proyectos de Generación de Conocimiento. Estudiando la  funcion, mecanismo y consecuencias de la inflammacion por card14. Bases para el diseño de mejores terapias para la psoriasis y sus comorbilidades. 2021-2026

NEA22-CRG168. National Eczema Asssociation (USA). CARD14 signaling in atopic dermatitis. 2023-2025

CR32023-040089. Consolidación investigadora 2024. Learning CARD14 unexplored physiopathological mechanisms and new ways to block it. (TAPIOCA: Treating Atopic dermatitis and Psoriasis by Inhibition Of CArd14). 2025-2027

Knödlseder N, Fábrega MJ, Santos-Moreno J, Manils J, Toloza L, Marín Vilar M, Fernández C, Broadbent K, Maruotti J, Lemenager H, Carolis C, Zouboulis CC, Soler C, Lood R, Brüggemann H, Güell M. Delivery of a sebum modulator by an engineered skin microbe in mice. Nat Biotechnol. 2024 

 

O'Sullivan PA, Aidarova A, Afonina IS, Manils J, Thurston TLM, Instrell R, Howell M, Boeing S, Ranawana S, Herpels MB, Chetian R, Bassa M, Flynn H, Frith D, Snijders AP, Howes A, Beyaert R, Bowcock AM, Ley SC. CARD14 signalosome formation is associated with its endosomal relocation and mTORC1-induced keratinocyte proliferation. Biochem J. 2024 

 

Bespalov D, Pino D, Vidal-Guirao S, Franquesa J, Lopez-Ramajo D, Filgaira I, Wan L, O'Sullivan PA, Ley SC, Forcales SV, Rojas JJ, Izquierdo-Serra M, Soler C, Manils J. Bioinformatic analysis of molecular characteristics and oncogenic features of CARD14 in human cancer. Sci Rep. 2024 

 

Kane LE, Flood B, Manils J, McSkeane DE, Smith AP, Tosetto M, Alalawi F, Fay J, Kay E, Dunne C, McQuaid S, Loughrey MB, O'Sullivan J, Ryan EJ, Sheahan K, Doherty GA, Creagh EM. Caspase-4 Has Potential Utility as a Colorectal Tissue Biomarker for Dysplasia and Early-Stage Cancer. Gastro Hep Adv. 2024 

 

Llorente X, Esteruelas G, Bonilla L, Agudelo MG, Filgaira I, Lopez-Ramajo D, Gong RC, Soler C, Espina M, García ML, Manils J, Pujol M, Sánchez-López E. Riluzole-Loaded Nanostructured Lipid Carriers for Hyperproliferative Skin Diseases. Int J Mol Sci. 2023

 

Manils J, Marruecos L and Soler C. Exonucleases: Degrading DNA to Deal with Genome Damage, Cell Death, Inflammation and Cancer. Cells. 2022. 

 

Marruecos L, Manils J, Moreta C, Gómez D, Filgaira I, Serafin A, Cañas X, Espinosa L, Soler C. Single loss of a Trp53 allele triggers an increased oxidative, DNA damage and cytokine inflammatory responses through deregulation of IκBα expression. CDDis. 2021. 

 

Manils J*, Webb V*, Howes A, Janzen J, Boeing S, Bowcock AM & Ley SC. CARD14E138A signalling in keratinocytes induces tnf-dependent skin and systemic inflammation. eLife, 2020. 

 

Kenealy S*, Manils J*, Raverdeau M, Munoz-Wolf N, Barber G, Liddicoat A, Lavelle EC, Creagh EM. Caspase-11-Mediated Cell Death Contributes to the Pathogenesis of Imiquimod-Induced Psoriasis. Journal of Investigative Dermatology, 2019. 

 

Flood B*, Manils J*, Nulty C, Flis E, Kenealy S, Barber G, Fay J, Mills KHG, Kay EW, Creagh EM. Caspase-11 Regulates the Tumour Suppressor Function of STAT1 in a Murine Model of Colitis-Associated Carcinogenesis. Oncogene, 2019. 

 

Manils J*, Fischer H*, Climent J, Casas E, García-Martínez C, Bas J, Sukseree S, Vavouri T, Ciruela F, de Anta JM, Tschachler E, Eckhart L, Soler C. Double deficiency of Trex2 and DNase1L2 nucleases leads to accumulation of DNA in lingual cornifying keratinocytes without activating inflammatory responses. Scientific Reports, 2017. 

 

Manils J, Casas E, Viña-Vilaseca A, López-Cano M, Díez-Villanueva A, Gómez D, Marruecos L, Ferran M, Benito C, Perrino FW, Vavouri T, de Anta JM, Ciruela F and Soler C. The exonuclease TREX2 shapes psoriatic phenotype. Journal of Investigative Dermatology, 2016. 

 

Dayana Pino Jimenez. PhD Student

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