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World J Hepatol. Mar 27, 2026; 18(3): 115111
Published online Mar 27, 2026. doi: 10.4254/wjh.v18.i3.115111
Published online Mar 27, 2026. doi: 10.4254/wjh.v18.i3.115111
From steatosis to inflammation: Innate lymphocytes as hidden orchestrators in metabolic dysfunction-associated steatotic liver disease
Cesar A San Juan-Garcia, Rita I Escamilla, Doctorado en Ciencias Biomédicas, Centro Uni
Lucia Cruz-Romero, Instituto de Investigación en Inmunología, Departamento de Fisiología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico
Christian D Hernandez-Silva, Departamento de Microbiologia y Patologia, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico
David Fernandez-Quezada, Instituto de Neurociencias Traslacionales, Departamento de Neu
Ulises De la Cruz-Mosso, Red de Inmunonutrición y Genómica Nutricional en las Enfer
Ana L Pereira-Suarez, Instituto de Investigación en Cancer e Infecciones, Departamento de Microbiología y Patología, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico
Jesse Haramati, Laboratorio de Inmunobiología, Departamento de Biología Celular y Mole
Inocencia G Ramirez-Lopez, Jose Macias-Barragan, Departamento de Ciencias de la Salud, Centro Universitario de los Valles, Universidad de Guadalajara, Ameca 46600, Jalisco, Mexico
Margarita Montoya-Buelna, Instituto de Investigación en Inmunología, Departamento de Fisiología, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico
Co-first authors: Cesar A San Juan-Garcia and Rita I Escamilla.
Author contributions: San Juan-Garcia CA and Escamilla RI contributed equally to this manuscript and are co-first authors; they conceptualized and designed the review, performed the main literature search, drafted the manuscript, created the figure, and made critical revisions; Cruz-Romero L and Hernandez-Silva CD participated in the literature search and contributed to manuscript drafting and editing; Fernandez-Quezada D assisted in organizing the review and drafting specific sections; De la Cruz-Mosso U and Pereira-Suarez AL contributed to the integration of references, refinement of the discussion, and provided critical input to the manuscript; Haramati J reviewed and corrected the English language; Ramirez-Lopez IG contributed to critical revision and provided academic feedback; Macias-Barragan J and Montoya-Buelna M supervised the project, provided guidance throughout, and made substantial revisions. All authors approved the final version of the manuscript.
Supported by Centro Universitario de Ciencias de la Salud Universidad de Guadalajara, Programa de Impulso a la Investigación, No. PIN 2024-V; and the Universidad de Guadalajara, Programa de Apoyo a la Mejora en las Condiciones de Producción de los Miembros del SNI y SNCA, No. PROSNII-2025.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Margarita Montoya-Buelna, Principal Investigator, Professor, Researcher, Instituto de Investigación en Inmunología, Departamento de Fisiología, Universidad de Guadalajara, Sierra Mojada 950, Guadalajara 44340, Jalisco, Mexico. margarita.montoya@academicos.udg.mx
Received: October 10, 2025
Revised: November 12, 2025
Accepted: January 6, 2026
Published online: March 27, 2026
Processing time: 168 Days and 16.8 Hours
Revised: November 12, 2025
Accepted: January 6, 2026
Published online: March 27, 2026
Processing time: 168 Days and 16.8 Hours
Core Tip
Core Tip: Metabolic dysfunction-associated steatotic liver disease is now recognized as a leading cause of chronic liver disease worldwide. Beyond metabolic stress and hepatocellular injury, recent evidence highlights the critical involvement of innate and innate-like lymphocytes, such as gamma delta T cells, natural killer cells, natural killer T cells, innate lymphoid cells, and mucosal-associated invariant T cells in driving inflammation, hepatocyte injury, and hepatic stellate cell activation. Depending on the microenvironment, these cells may exert protective or pathogenic roles, shaping progression toward steatohepatitis and fibrosis. Understanding their effector functions offers opportunities for novel biomarkers and therapeutic strategies in metabolic dysfunction-associated steatotic liver disease.