Fig. 2: Neurons and oligodendrocytes are molecularly equipped to sense IL-12.

a, Schematic of the mouse cerebellum showing the region represented by the following images. b–d, Immunostaining of β-gal⁺Calbindin⁺ and β-gal⁺NeuN⁺ cells in the steady-state cerebellum of Il12rb2^LacZ/LacZ reporter mice (n = 6 mice, m/f; data are representative for one of three experiments) and β-gal⁻NeuN⁺ cells in control C57BL/6 mice. e, Schematic of the mouse hippocampus showing region represented by the following images. f–h, Immunostaining of β-gal⁺NeuN⁺, βgal⁻GFAP⁺ and β-gal⁺ CC1⁺ cells in the hippocampal and cortical region of steady-state Il12rb2^LacZ/LacZ reporter mice (n = 5 mice, m/f; data are representative for one of three experiments) and β-gal⁻NeuN⁺ cells in control C57BL/6 mice. In b–d and f–h, scale bars indicate 50 μm or 100 μm. Insets are enlargements of outlined regions in the original images. i, Schematic of the mouse cerebrum showing the region represented by the following images. j, Multiplexed single-molecule RNA fluorescence in situ hybridization (RNAscope) in steady-state C57BL/6 mouse cerebral tissue showing Il12rb2 gene coexpression in Map2⁺Rbfox3⁺ neurons and Il12rb1 coexpression in Sox10⁺ oligodendrocytes. Scale bars, 25 μm. k, Il12rb1 and Il12rb2 mRNA expression of CD45⁻CD11b⁻O4⁻ACSA-2⁺astrocytes, CD45^loCD44^loCD11b⁺CX3CR1⁺ microglia, CD45⁻CD11b⁻ACSA-2⁻ O4⁺ oligodendrocytes, NK cells and CD3⁺ T cells isolated by FACS from the CNS of C57BL/6 mice at peak EAE (n = 4–10, m/f; number of dots represents the number of biologically independent replicates per sample; 14 d.p.i.). Data are shown as the mean ± s.e.m. Kruskal–Wallis test, corrected Dunn’s test (**P = 0.0012; ** P = 0.0016; ***P = 0.0009; *P = 0.0391; **P = 0.0052, left to right). l, Il12rb1 and Il12rb2 mRNA expression of Hoechst⁺ Olig2⁺ oligodendrocyte nuclei and Hoechst⁺ NeuN⁺ neuronal nuclei isolated by FANS from the CNS of C57BL/6 mice (n = 5–7; number of dots represents the number of biologically independent replicates per sample) at peak EAE (14 d.p.i.). Data are shown as mean ± s.e.m. (unpaired two-tailed Mann–Whitney test, **P = 0.0293, P = 0.1282, left to right). m, Schematic of human MS brain lesions (created with BioRender.com). n, Representative immunofluorescence of IL-12Rβ2-expressing MAP2⁺ neurons in brain tissue samples from individuals with MS (n = 3; data representative for one of three experiments). Scale bars, 20 μm and 100 μm. Lower images depict enlargements of outlined regions in the original (top) images. Gcl, granule cell layer; ml, molecular layer; pcl, Purkinje cell layer; sg (DG-sg), dentate gyrus, granule cell layer; po (DG-po), dentate gyrus, polymorph layer; mo (DG-mo), dentate gyrus, molecular layer; m, male; f, female.

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