Peripheral monocytes from Crohn's disease patients retain functional responsiveness to GM-CSF during active disease.

Introduction: Crohn's disease (CD) is a relapsing inflammatory disease that is currently not curable. Despite the availability of anti-inflammatory treatments, 30-60% 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. Methods: 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. Results: 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 naïve 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. Discussion: 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.