02527nas a2200301 4500000000100000000000100001008004100002260001500043653001400058653001900072653002500091653001600116653002000132100002500152700001600177700001900193700002100212700002700233700002200260700001700282700002500299700002700324245012700351856009300478490000700571520163300578022001402211 2023 d c2023-10-1310aCytokines10aflow cytometry10aImmunohistochemistry10aMacrophages10aimmune response1 aPatrick P. G. Mulder1 aMarcel Vlig1 aAnouk Elgersma1 aLotte Rozemeijer1 aLeonore S. Mastenbroek1 aEsther Middelkoop1 aIrma Joosten1 aHans J. P. M. Koenen1 aBouke K. H. L. Boekema00aMonocytes and T cells incorporated in full skin equivalents to study innate or adaptive immune reactions after burn injury uhttps://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1264716/full0 v143 aIntroduction

Thermal injury often leads to prolonged and excessive inflammation, which hinders the recovery of patients. There is a notable absence of suitable animal-free models for investigating the inflammatory processes following burn injuries, thereby impeding the development of more effective therapies to improve burn wound healing in patients.

Methods

In this study, we established a human full skin equivalent (FSE) burn wound model and incorporated human peripheral blood-derived monocytes and T cells.

Results

Upon infiltration into the FSEs, the monocytes differentiated into macrophages within a span of 7 days. Burn-injured FSEs exhibited macrophages with increased expression of HLA-DR+ and elevated production of IL-8 (CXCL8), in comparison to uninjured FSEs. Among the T cells that actively migrated into the FSEs, the majority were CD4+ and CD25+. These T cells demonstrated augmented expression of markers associated with regulatory T cell, Th1, or Th17 activity, which coincided with significant heightened cytokine production, including IFN-γ, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IP-10 (CXCL10), and TGF-β1. Burn injury did not impact the studied effector T cell subsets or cytokine levels.

Discussion

Collectively, this study represents a significant advancement in the development of an immunocompetent human skin model, specifically tailored for investigating burn-induced innate or adaptive immune reactions at the site of burn injury.

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