Assessment of dermal sensitization by nickel salts in a novel humanized TLR-4 mouse model
The fundamental goal of this study was to determine the potential utility of a novel humanized Toll-like receptor-4 (hTLR-4) mouse model for future in vivo studies of nickel allergy. First, mice of both sexes and hTLR-4 expression profiles were incorporated into a Local Lymph Node Assay (LLNA) to as...
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Taylor & Francis Group
2024-12-01
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| Series: | Journal of Immunotoxicology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/1547691X.2024.2414979 |
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| author | K. A. Roach S. E. Anderson C. Waggy J. Aldinger A. B. Stefaniak J. R. Roberts |
| author_facet | K. A. Roach S. E. Anderson C. Waggy J. Aldinger A. B. Stefaniak J. R. Roberts |
| author_sort | K. A. Roach |
| collection | DOAJ |
| description | The fundamental goal of this study was to determine the potential utility of a novel humanized Toll-like receptor-4 (hTLR-4) mouse model for future in vivo studies of nickel allergy. First, mice of both sexes and hTLR-4 expression profiles were incorporated into a Local Lymph Node Assay (LLNA) to assess skin sensitization. Next, a set of hTLR-4 hTLR-4-positive mice (female and male groups) was similarly exposed to vehicle control (VC) or 10% NiSO4 on Days 1, 2, and 3. Mice were euthanized on Day 10, lymph node (LN) cellularity was assessed, LN and spleen cells were phenotyped, and serum was collected to quantify circulating cytokine and IgE levels. In the LLNA, hTLR-4-positive mice of both sexes exhibited enhanced responsivity to nickel. NiSO4 (10%) had a stimulation index (SI) of 3.7 (females) and 3.8 (males) in hTLR-4-positive animals, and an SI of 0.5 (females) and 0.8 (males) in hTLR-4 hTLR-4-negative mice. In the 10d study, hTLR-4-positive mice exposed to 10% NiSO4 exhibited increased LN cellularity (6.0× increase in females, 3.2× in males) and significantly higher concentrations of circulating IgE (4.1× increase in females, 3.4× in males). Significant increases in serum interferon (IFN)-γ, interleukin (IL)-4, and IL-5 levels were seen in female mice, while altered concentrations of IL-4 and IL-10 were detected in male mice. The results of this study ultimately demonstrate that murine expression of hTLR-4 confers enhanced susceptibility to dermal sensitization by nickel, and consequently, the hTLR-4 mouse model represents a viable approach for future studies of nickel allergy in vivo. |
| format | Article |
| id | doaj-art-ce4691116888410f8eeb3046ba7bbfbf |
| institution | Kabale University |
| issn | 1547-691X 1547-6901 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Immunotoxicology |
| spelling | doaj-art-ce4691116888410f8eeb3046ba7bbfbf2025-01-17T12:52:14ZengTaylor & Francis GroupJournal of Immunotoxicology1547-691X1547-69012024-12-0121110.1080/1547691X.2024.2414979Assessment of dermal sensitization by nickel salts in a novel humanized TLR-4 mouse modelK. A. Roach0S. E. Anderson1C. Waggy2J. Aldinger3A. B. Stefaniak4J. R. Roberts5Allergy and Clinical Immunology Branch (ACIB), National Institute of Occupational Safety and Health (NIOSH), Morgantown, WV, USAAllergy and Clinical Immunology Branch (ACIB), National Institute of Occupational Safety and Health (NIOSH), Morgantown, WV, USAOffice of the Director, NIOSH, Morgantown, WV, USAAllergy and Clinical Immunology Branch (ACIB), National Institute of Occupational Safety and Health (NIOSH), Morgantown, WV, USARespiratory Health Division, NIOSH, Morgantown, WV, USAAllergy and Clinical Immunology Branch (ACIB), National Institute of Occupational Safety and Health (NIOSH), Morgantown, WV, USAThe fundamental goal of this study was to determine the potential utility of a novel humanized Toll-like receptor-4 (hTLR-4) mouse model for future in vivo studies of nickel allergy. First, mice of both sexes and hTLR-4 expression profiles were incorporated into a Local Lymph Node Assay (LLNA) to assess skin sensitization. Next, a set of hTLR-4 hTLR-4-positive mice (female and male groups) was similarly exposed to vehicle control (VC) or 10% NiSO4 on Days 1, 2, and 3. Mice were euthanized on Day 10, lymph node (LN) cellularity was assessed, LN and spleen cells were phenotyped, and serum was collected to quantify circulating cytokine and IgE levels. In the LLNA, hTLR-4-positive mice of both sexes exhibited enhanced responsivity to nickel. NiSO4 (10%) had a stimulation index (SI) of 3.7 (females) and 3.8 (males) in hTLR-4-positive animals, and an SI of 0.5 (females) and 0.8 (males) in hTLR-4 hTLR-4-negative mice. In the 10d study, hTLR-4-positive mice exposed to 10% NiSO4 exhibited increased LN cellularity (6.0× increase in females, 3.2× in males) and significantly higher concentrations of circulating IgE (4.1× increase in females, 3.4× in males). Significant increases in serum interferon (IFN)-γ, interleukin (IL)-4, and IL-5 levels were seen in female mice, while altered concentrations of IL-4 and IL-10 were detected in male mice. The results of this study ultimately demonstrate that murine expression of hTLR-4 confers enhanced susceptibility to dermal sensitization by nickel, and consequently, the hTLR-4 mouse model represents a viable approach for future studies of nickel allergy in vivo.https://www.tandfonline.com/doi/10.1080/1547691X.2024.2414979Nickeltoll-like receptor-4local lymph node assayhypersensitivityallergy modelsensitization |
| spellingShingle | K. A. Roach S. E. Anderson C. Waggy J. Aldinger A. B. Stefaniak J. R. Roberts Assessment of dermal sensitization by nickel salts in a novel humanized TLR-4 mouse model Journal of Immunotoxicology Nickel toll-like receptor-4 local lymph node assay hypersensitivity allergy model sensitization |
| title | Assessment of dermal sensitization by nickel salts in a novel humanized TLR-4 mouse model |
| title_full | Assessment of dermal sensitization by nickel salts in a novel humanized TLR-4 mouse model |
| title_fullStr | Assessment of dermal sensitization by nickel salts in a novel humanized TLR-4 mouse model |
| title_full_unstemmed | Assessment of dermal sensitization by nickel salts in a novel humanized TLR-4 mouse model |
| title_short | Assessment of dermal sensitization by nickel salts in a novel humanized TLR-4 mouse model |
| title_sort | assessment of dermal sensitization by nickel salts in a novel humanized tlr 4 mouse model |
| topic | Nickel toll-like receptor-4 local lymph node assay hypersensitivity allergy model sensitization |
| url | https://www.tandfonline.com/doi/10.1080/1547691X.2024.2414979 |
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