Biology subjects

Chang, A. A.

Publications and source records attributed to Chang, A. A..

2 recordsLinked to original sources

bioRxiv2024

Dynamic fibroblast-immune interactions shape wound healing after brain injury

Fibroblasts coordinate the response to tissue injury, directing organ regeneration versus scarring. In the central nervous system (CNS), fibroblasts are uncommon cells enriched at tissue borders, and their molecular, cellular, and functional interactions after brain injury are poorly understood. Here we define the fibroblast response to sterile brain damage across time and space. Early pro-fibrotic myofibroblasts infiltrated CNS lesions and were functionally and spatially organized by fibroblast TGF{beta} signaling, pro-fibrotic macrophages and microglia, and perilesional brain glia that activated TGF{beta} via integrin v{beta}8. Early myofibroblasts subsequently transitioned into a variety of late states, including meningeal and lymphocyte-interactive fibroblasts that persisted long term. Interruption of this dynamic fibroblast-macrophage-glial coordination impaired brain wound healing and the resolution of neuroinflammation, disrupted generation of late de novo CNS lymphocyte niches, and increased mortality in a stroke model. This work highlights an unexpected role of fibroblasts as coordinate regulators of CNS healing and neuroinflammation after brain injury.

immunology↗

bioRxiv2023

Group 2 innate lymphoid cells constrain type 3/17 lymphocytes in shared stromal niches to restrict liver fibrosis

Group 2 innate lymphoid cells (ILC2s) cooperate with adaptive Th2 cells as key organizers of tissue type 2 immune responses, while a spectrum of innate and adaptive lymphocytes coordinate early type 3/17 immunity. Both type 2 and type 3/17 lymphocyte associated cytokines are linked to tissue fibrosis, but how their dynamic and spatial topographies may direct beneficial or pathologic organ remodelling is unclear. Here we used volumetric imaging in models of liver fibrosis, finding accumulation of periportal and fibrotic tract IL-5+ lymphocytes, predominantly ILC2s, in close proximity to expanded type 3/17 lymphocytes and IL-33high niche fibroblasts. Ablation of IL-5+ lymphocytes worsened carbon tetrachloride-and bile duct ligation-induced liver fibrosis with increased niche IL-17A+ type 3/17 lymphocytes, predominantly {gamma}{delta} T cells. In contrast, concurrent ablation of IL-5+ and IL-17A+ lymphocytes reduced this progressive liver fibrosis, suggesting a cross-regulation of type 2 and type 3 lymphocytes at specialized fibroblast niches that tunes hepatic fibrosis.

immunology↗