Volume 151, Issue 5, Pages 780-783 (November 2016) Focal and Local: Ectopic Lymphoid Structures and Aggregates of Myeloid and Other Immune Cells in Liver  Eli Pikarsky  Gastroenterology  Volume 151, Issue 5, Pages 780-783 (November 2016) DOI: 10.1053/j.gastro.2016.09.029 Copyright © 2016 AGA Institute Terms and Conditions

Figure 1 Ectopic lymphoid structures in human and murine liver. A, Hematoxylin and eosin staining of a hepatic ectopic lymphoid structures (ELS) derived from a patient with chronic hepatitis B virus infection (with courtesy from Prof. Achim Weber). The follicle-like structure and organization similar to a white pulp follicle in the spleen is visible. Scale bar: 50 μm. A, right, Hepatic ELS of a mouse liver with a constitutive activation of the nuclear factor κB signaling pathway in hepatocytes of IKKβ(E/E)Hep mice2. Scale bar: 100 μm. Arrow head indicates aberrant hepatocytes in an ELS. B, Three-dimensional (3D) reconstruction of a murine ELS from a 6-month-old DEN-treated IKKβ(EE)Hep mouse. B, Left, Double color immunostaining for CD44v6 (brown for liver cancer progenitor cells) and B220 (red for B-lymphocytes) in 2 dimensions. B, middle, A 3D reconstruction (top view) and color conversion of the left panel (brown to green, red to purple). B, right, A 3D reconstruction side view. Note green CD44v6+ progenitor cell aggregates that egress out of the ELS in multiple points. The α, β, and γ indicate the same region in all panels (scale bar: 100 μm). Figures are adapted from2. C, Histologic characterization of myeloid cells in intrahepatic myeloid aggregates for T-cell expansion (iMATES) upon induction with a Toll-like receptor (TLR)-9 agonist (CpG-ODN) or a control (ctrl). High focal TNF expression and up-regulation of iNOS can be found on MHCII expressing myeloid cells within iMATES. Scale bar low resolution (left 2 columns): 100 μm. Scale bar high resolution (right column): 10 μm. Figures adapted from4. iNOS, inducible nitric oxide synthase; MHCII, major histocompatibility complex class II; TLR-9-L, Toll-like receptor 9 ligand (CpG-ODN); TNF, tumor necrosis factor alpha. D, A 3D reconstruction of an iMATE, represented by a myeloid cocoon-like structure (purple) with locally expanding and proliferating T cells (green). Scale bar: 25 μm. Gastroenterology 2016 151, 780-783DOI: (10.1053/j.gastro.2016.09.029) Copyright © 2016 AGA Institute Terms and Conditions