Fig 2: STEAP1 CAR design and expression(A) Schematic of STEAP1 CAR from N terminus to C terminus: signal peptide, RQR8, 2A self-cleavage peptide, signal peptide for the CAR, Oslo1 scFv targeting STEAP1, CD8a hinge domain, CD8a transmembrane domain, 4-1BB co-stimulatory domain, and CD3ζ intracellular signaling domain. (B) T cells were surface stained for CD3, CD4, and CD8 (left and middle) and analyzed by flow cytometry. CAR expression was identified by RQR8 staining. Histograms to the right show STEAP1 CAR-transduced (gray filled) CD4+ and CD8+ T cells, overlaid with NT T cells (black open). (C) The expression of the STEAP1 CAR and a CD19-specific CAR with an identical backbone was measured in transduced T cells from 10 healthy donors. Error bars indicate SD.

Fig 3: In vitro migration assay. Insulin-like growth factor binding protein 6 (IGFBP6) is able to induce the migration of rheumatoid arthritis (RA) but not healthy donors (HD) and osteoarthritis (OA) peripheral blood mononuclear cells (A). The addition of dexamethasone (dex) in the upper chamber of the transwell partly inhibited such RA cell migration (B). The majority of RA-migrated cells are CD3+ T lymphocytes (C) and the addition of dex does not affect the proportion of migrated cells (D). All p values are calculated with Mann–Whitney U test.

Fig 4: Highly proliferative cells in islets of ANGPTL8 treated mice are not immune related cells.Immunostaining for EdU (green) and DAPI (blue), with various markers for immune-related cells (red) in (a,c,e,g,i) pancreatic islets or in (b,d,f,h,j) the spleen used as a positive control. (a-b) CD3 (T-cells), (c-d) B220 (B-Cells), (e-f) F480 (macrophages), (g-h) CD11c (dendritic cells), and (i- j) Gr-1 (Neutrophils). Insets indicate an EdU+ replicating cell that does not express CD3, B220, F480, CD11c, or Gr-1. Scale bar = 100 μm.

Fig 5: Results of gross pathological, histopathological, histochemical, and immunohistochemical investigation of canine chronic cholecystitis. (a) Ultrasonography revealed sandy, gravity-dependent contents interpreted as sludge (asterisk). Case 122. Bar = 2 cm. (b) Sludge is dark brown, viscous material. Case 12. (c) Filaments and rods are present within gallbladder content. Warthin–Starry (WS). Case 1. Bar = 50 µm. (d) Rods and coccobacilli are present within gallbladder content. WS. Case 169. Bar = 50 µm. (e). The material ultrasonographically and grossly described as “sludge” is histologically composed of fragmented mucus (arrows) and microliths (arrowheads). Hematoxylin and eosin (HE). Case 57. Bar = 500 µm. (f) The lamina propria is expanded by heavy infiltrates of lymphocyte and plasma cell, interpreted as grade 2 (G2) inflammation. HE. Case 164. Bar = 200 µm. Inset: higher magnification of lymphocytes and plasma cells in the lamina propria of the gallbladder of the same dog. (g) Chronic cholecystitis. CD20-positive B cells predominate. Immunohistochemistry (IHC). Case 19. Bar = 125 µm. (h). Chronic cholecystitis. A few MUM1-positive plasma cells are present. IHC. Case 19. Bar = 125 µm. (i) Chronic cholecystitis. A few CD3-positive T cells are present. IHC. Case 19. Bar = 125 µm. (j) Chronic cholecystitis. Granzyme-B-positive cells are not present. IHC. Case 19. Bar = 125 µm. (k) Lymphoid follicle has a prominent germinal center. HE. Case 19. Bar = 500 µm. (l) Many CD20-positive B cells are present in the germinal center (asterisk) and marginal zone. IHC. Case 19. Bar = 250 µm. (m) A few MUM1-positive plasma cells are present in the perifollicular area (arrows). IHC. Case 19. Bar = 250 µm. (n) Few CD3-positive T cells are present in the mantle zone and perifollicular area. IHC. Case 19. Bar = 250 µm. (o) Granzyme-B-positive cells are not present. IHC. Case 19. Bar = 250 µm.