Abstract
Diabetes, as a chronic metabolic disease, can impair the immune function of monocytes/macrophages (MMs). However, it is unclear how MMs immune response to inflammation with the development of diabetes, and whether immune response around the inflammatory foci depends on the depth in tissue. Footpad provides a classical physiological site for monitoring cellular behavior during inflammation, but limited to the superficial dermis due to the strong scattering of footpad. Herein, we used confocal microscopy to monitor the motility of MMs in deeper tissue around inflammatory foci with the development of type 1 diabetic (T1D) mice through a swithable footpad skin optical clearing window. Delayed-type hypersensitivity (DTH) model was elicited on the footpad of T1D. Results demonstrated that progressive T1D led to the gradually potentiated MMs recruitment and increased expression of monocyte chemoattractant protein-1 during DTH, but MMs migration displacement, motion velocity and motility coefficient were significantly attenuated. Besides, MMs from the deeper dermis had a much larger migration displacement than those from superficial dermis at early stages of DTH but an opposite tendency at late stages for non-T1D, while progressive T1D obscured this difference gradually. This study will be helpful for investigating the influences of progressive metabolic diseases on immune response. MMs motion trajectory at depth of superficial dermis and the deeper dermis at AOVA-4h and AOVA-72h on Non-T1D (A) and T1D-4w (B). Mean motility coefficient (C) at the two depths. Data were pooled from 6 mice per group. * (p < 0.05) and ** (p < 0.01) compared among different T1D disease durations. # (p < 0.05) compared between different depths.
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