Fig. 1: Deletion of IL-12-specific receptor subunit IL12Rβ2 results in reduction of amyloid burden. | Nature Aging

Fig. 1: Deletion of IL-12-specific receptor subunit IL12Rβ2 results in reduction of amyloid burden.

From: Interleukin-12 signaling drives Alzheimer’s disease pathology through disrupting neuronal and oligodendrocyte homeostasis

Fig. 1

a, p40 can form monodimers (IL-12p80) or heterodimers (IL-12p70) consisting of p35 and p40. IL-12p70 binds to the dimerized IL-12Rβ2 and IL-12Rβ1. IL-23, consisting of p19 and p40, binds to the receptor subunits IL-23R and IL-12Rβ1. The genes that encode the respective protein subunits are shown in matched color. This illustration was created in BioRender: Geesdorf, M. (2025) https://BioRender.com/w20e262. b,c, By crossbreeding either Il12rb2fl/fl or Il23rfl/fl mice to APPPS1 and to NestinCre animals, IL-12-specific or IL-23-specific receptor deletion was achieved in neuroectodermal cells of AD-like mice. This illustration was created in BioRender: Geesdorf, M. (2025) https://BioRender.com/m33j769 and https://BioRender.com/q27e982. d, Proteins from total brains of 250-day-old APPPS1.NestinCre.Il12rb2fl/fl mice (n = 9) and APPPS1 littermates expressing functional Il12rb2 (n = 9) were extracted based on their solubility and assessed for Aβ1–40 and Aβ1–42 in the soluble (TBS) and insoluble (Triton-X and SDS) fractions using an electrochemiluminescence ELISA assay (Meso Scale). Aβ1–40: t = 3.062, df = 16, **P = 0.0075 for the TBS fraction; t = 3.256, df = 16, **P = 0.0050 for the TX fraction; and t = 2.034, df = 11, P = 0.668 for the SDS fraction; Aβ1–42: unpaired t-tests, t = 0.5092, df = 16, P = 0.6175 for the TBS fraction; t = 0.3554, df = 16, P = 0.7269 for the TX fraction; and t = 1.627, df = 11, P = 0.1319 for the SDS fraction. e, Aβ1–40 and Aβ1–42 levels in APPPS1.NestinCre.Il23rfl/fl mice (n = 9) and APPPS1 littermates with functional IL-23 receptor subunit (n = 9) upon similar workup as described in d; Aβ1–40: t = 0.7989, df = 14, P = 0.4377 for the TBS fraction; t = 0.4474, df = 16, P = 0.6606 for the TX fraction; and t = 1.393, df = 15, P = 0.1838 for the SDS fraction; Aβ1–42: t = 1.710, df = 16, P = 0.1066 for the TBS fraction; t = 0.1808, df = 16, P = 0.8588 for the TX fraction; and t = 0.3960, df = 16, P = 0.69731 for the SDS fraction. Data were analyzed as two-tailed unpaired t-test; bars represent mean ± s.e.m. df, degrees of freedom; NS, not significant.

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