Gawor, J.; Deinzer, A.; Wick, M.; Hayek, I.; Schwartz, C.

Background: Obesity disrupts type 2 immune cell populations in white adipose tissue, replacing the homeostatic network of group 2 innate lymphoid cells (ILC2s), eosinophils, T helper 2 (Th2) cells, and alternatively activated macrophages (AAMs) with pro-inflammatory type 1 populations. Whether this remodelling reflects permanent immune impairment or a reversible shift in cellular equilibrium, and to what extent bariatric surgery restores type 2 immunity, remain incompletely understood. Methods: We performed comprehensive immunophenotyping of visceral white adipose tissue (WAT) and peripheral blood from persons with severe obesity (people with obesity, PWO) scheduled for or having undergone bariatric surgery (sleeve gastrectomy, gastric bypass), combined with lean controls. Using flow cytometry, quantitative PCR, and in vitro polarization assays, we assessed immune cell frequencies, transcription factor expression, cytokine profiles, and functional polarization capacity across lean, pre-operative, and post-operative states. Results: Obesity was associated with decreased eosinophil and CD8+ T cells frequencies in WAT, accompanied by an increase in CD4+ frequency and a shift from Th2 toward Th1 predominance, as well as elevated PD-1 expression on T cell subsets. Bariatric surgery partially normalised peripheral immune cell composition, notably reducing CD8+ and CD4+ T cell frequencies. Critically, in vitro polarization demonstrated that naive CD4+ T cells from PWO retained Th2 polarization capacity, monocyte-derived macrophages maintained AAM differentiation potential, and eosinophils responded robustly to IL-5 stimulation. Sex-stratification revealed increased activity of eosinophils in females. Conclusion: Type 2 immune cells retain functional plasticity in human obesity despite reduced frequency. Bariatric surgery partially reconstitutes immune functionality, suggesting that obesity creates a persistent inflammatory imprint amenable to targeted immunomodulatory intervention. Funding: German Federal Ministry of Research, Technology and Space (BMFTR, FKZ 01KI2109), Interdisciplinary Center for Clinical Research (IZKF, Faculty of Medicine, Friedrich-Alexander Universitat (FAU) Erlangen-Nurnberg).