PMC8374102_01
APRIL targets reactive astrocytes in NMO lesions. Serial sections of a NMO biopsy harboring an active lesion were immunostained. (A) shows a widespread loss of aquaporin 4 (AQP4) associated to preservation of aquaporin 1 (AQP1), and proteolipid protein (PLP)-positive myelin sheaths. A vasculocentric (rosette-like) deposition of activated complement (C9 neo) is observed in an active lesion area rich in polymorphonuclear cells (scale bar = 100 mum). The central canal (CC) of the spinal cord and a polymorphonuclear cell (arrow) are indicated. (B) shows merge stainings for CD68+ myeloid cells and APRIL-producing cells (APRIL p.) (scale bar = 10 mum). Arrow and arrowhead mark APRIL+ and APRIL- CD68+ myeloid cells, respectively. Right panel shows a high magnification of APRIL-producing cells with a macrophage (top figure) and polymorphonuclear (bottom figure) morphology (scale bar = 5 mum). (C) shows in meninges associated to the lesion stainings for plasmocytes (CD138), APRIL p. and secreted APRIL (APRIL s.) (scale bar = 10 mum). Upper panels (D) show in the parenchyma stainings for APRIL p. and APRIL s. (scale bar = 100 mum). Cells binding APRIL with a morphology of astrocytes are arrowed, showed in the high magnification insert (scale bar, 5 mum), and identified by GFAP costaining (scale bar = 5 mum). Lower panels (D) show an area outside lesions of the spinal cord stainings for APRIL p. and APRIL s. (scale bar 100 mum).
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F1
At the spinal cord level, typical pathological features of NMO were seen with a widespread loss of AQP4 within and around the lesions, while AQP1 reactivity was partially spared (Figure 1A). APRIL expression, we used the pair of antibodies identifying APRIL-producing cells and secreted APRIL in tissues. APRIL-producing cells were part of the CD68+ myeloid cell pool (Figure 1B). The common APRIL target cells, CD138+ plasmocytes, were sparsely distributed within meninges adjacent to lesions (Figure 1C). In the parenchyma, APRIL-producing cells were highly abundant, representing as much as 50% of the total cellularity in some area (Figure 1D upper panels). Accumulation of secreted APRIL in astrocytes was quite high, filling up the entire cytoplasmic space of the cells. APRIL-producing cells and secreted APRIL were absent outside lesions from this spinal cord (Figure 1D lower panels).