Figure 3.
Expression of IL-11 in chronic silent MS lesions. a–e, Localization of IL-11+ cells in MS tissue. Adjacent sections are shown of a chronic silent lesion from a 32-year-old female MS patient. a is a low-magnification photograph illustrating the extent of the lesion (L), whereas b–d show higher magnification views of an area of the lesion border stained for Luxol fast blue (LFB) (b), MBP (c), and IL-11 (d). b illustrates the morphology of this area; note the demyelination within the lesion (right side of the panel, pale pink), which contrasts with the presence of myelin in an adjacent area of more normal-appearing white matter (WM) (left side of panel, blue). Myelin appears as parallel blue lines and is present in the normal-appearing white matter and to a lesser extent at the lesion border (black arrows). A similar distribution for myelin is observed in c, immunostained for MBP. This panel also clearly illustrates a slight hypercellularity at the lesion border. Many of the cells in this area have small round nuclei characteristic of oligodendrocytes (green arrows). In d, immunostaining for IL-11 is seen to localize to large hypertrophic cells that resemble astrocytes (red arrows), with immunoreactivity concentrated at the lesion border, extending into more normal-appearing white matter. Note that minimal immunoreactivity for IL-11 is observed in the lesion itself. The distribution of IL-11 immunoreactivity is quantitated in e. wm, White matter; bor, border; les, lesion. f–i, Phenotypic identification of cells expressing IL-11 and IL-11Rα. A higher-magnification photograph of a typical IL-11+ cell is shown in f. This large, process-bearing cell has morphology similar to that of a hypertrophic astrocyte, and double-staining for IL-11 and GFAP confirms the identity of IL-11-expressing cells (g). No immunoreactivity for IL-11 was observed in microglia or oligodendrocytes. Immunostaining for the IL-11 ligand-specific receptor subunit IL-11Rα is shown in h. Immunoreactivity localized to small cells with round nuclei, with the morphological characteristics of oligodendrocytes. The identity of these cells was confirmed using double staining for IL-11Rα and the oligodendrocyte marker PDGFRα (i). Magnification: a, 30×; b–d, 100×; f–i, 500×. In e, error bars indicate SEM. ***p < 0.001, ANOVA followed by Bonferroni's post test.