{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T00:07:14Z","timestamp":1758672434917,"version":"3.44.0"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Crohn\u2019s disease (CD) is a relapsing inflammatory disease that is currently not curable. Despite the availability of anti-inflammatory treatments, 30\u201360% of patients develop resistance, necessitating the need for novel therapeutic approaches. Data from colitis models in mice indicate that granulocytemacrophage colony-stimulating factor (GM-CSF)-activated monocytes (GMaMs) may serve as a promising cellular therapy. However, it remains unclear whether inflammatory mediators, medication, or intrinsic defects impair the functionality of monocytes in active CD (aCD), potentially affecting their therapeutic efficacy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Monocytes from 8 aCD patients and healthy donors (HDs) were activated in vitro with GM-CSF, and their migratory capacity, adherence, metabolic activity, surface marker expression, and cytokine release were assessed. Cells were stimulated with lipopolysaccharides (LPS) to evaluate their inflammatory response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The GMaM phenotype was characterized by increased metabolic activity, enhanced production of inflammatory cytokines, stronger adhesion, and remodeling of surface receptors involved in T-cell activation, compared to na\u00efve monocytes. These features were largely comparable between aCD patients and HDs. LPS stimulation of GMaMs from both groups resulted in a significant production of pro-inflammatory and chemotactic cytokines, particularly interleukin (IL)-8 and monocyte chemotactic protein 1. Both are crucial recruiters of neutrophils and monocytes. Notably, monocytes from aCD patients showed an increased IL-10 response to GM-CSF, while the LPS-induced tumor necrosis factor-alpha and interferon-gamma release were reduced compared to HDs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Peripheral monocytes from aCD patients retain functional responsiveness to GM-CSF activation, displaying preserved migratory, adhesive, metabolic, and cytokine responses. Differences in cytokine production by aCD monocytes may reflect disease-specific regulation, but do not appear to limit their suitability as cellular therapeutics.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1663713","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T05:32:11Z","timestamp":1758605531000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Peripheral monocytes from Crohn\u2019s disease patients retain functional responsiveness to GM-CSF during active disease"],"prefix":"10.3389","volume":"16","author":[{"given":"Paul 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