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1.
Immunobiology ; 228(3): 152356, 2023 05.
Article in English | MEDLINE | ID: mdl-36857909

ABSTRACT

Perfluorooctane sulfonic acid (PFOS) is member of a class of molecules with fluorinated carbon chains known as polyfluoroalkyls. PFOS have been used to produce a variety of industry and comsumer uses. However, a significant concern is that it accumulates in the environment, including in animals and humans, and that it is a potential immunosuppressant. Here we analyze immune homeostasis in mice following chronic exposure to PFOS at levels up to those historically found in PFOS manufacturing workers. Mice were exposed to 0.15, 1.5, 15, or 50 µg /kg of PFOS for 28 days, after which, B cells, T cells, and granulocytes from the bone marrow, liver, spleen, lymph nodes, and thymus were evaluated. We find that at these exposures, there was no effect of PFOS on major T- or B-cell populations, macrophages, dendritic cells, basophils, mast cells, eosinophils, neutrophils, serum antibodies or select serum cytokines. By contrast, mice exposed the known immunosuppressant cyclophosphamide, which was given at 40 mg/kg for four days, exhibited depletion of several granulocyte, T- and B-cell populations of the thymus, bone marrow, and spleen, as well as circulating IgM and IgE antibodies. These data indicate that exposures of up to 50 µg /kg of PFOS for 28 days does not affect immune homeostasis in mice.


Subject(s)
Alkanesulfonic Acids , T-Lymphocytes , Humans , Mice , Animals , Cyclophosphamide/pharmacology , Alkanesulfonic Acids/pharmacology , Immunosuppressive Agents/pharmacology
2.
Commun Biol ; 5(1): 162, 2022 02 24.
Article in English | MEDLINE | ID: mdl-35210549

ABSTRACT

T helper 17 (Th17) cells develop in response to T cell receptor signals (TCR) in the presence of specific environments, and produce the inflammatory cytokine IL17A. These cells have been implicated in a number of inflammatory diseases and represent a potential target for ameliorating such diseases. The kinase ITK, a critical regulator of TCR signals, has been shown to be required for the development of Th17 cells. However, we show here that lung inflammation induced by Saccharopolyspora rectivirgula (SR) induced Hypersensitivity pneumonitis (SR-HP) results in a neutrophil independent, and ITK independent Th17 responses, although ITK signals are required for γδ T cell production of IL17A. Transcriptomic analysis of resultant ITK independent Th17 cells suggest that the SR-HP-induced extrinsic inflammatory signals may override intrinsic T cell signals downstream of ITK to rescue Th17 responses in the absence of ITK. These findings suggest that the ability to pharmaceutically target ITK to suppress Th17 responses may be dependent on the type of inflammation.


Subject(s)
Alveolitis, Extrinsic Allergic , Pneumonia , Protein-Tyrosine Kinases , Th17 Cells , Alveolitis, Extrinsic Allergic/enzymology , Alveolitis, Extrinsic Allergic/immunology , Alveolitis, Extrinsic Allergic/metabolism , Cytokines/metabolism , Humans , Inflammation/metabolism , Pneumonia/chemically induced , Pneumonia/enzymology , Pneumonia/immunology , Pneumonia/metabolism , Protein-Tyrosine Kinases/immunology , Th17 Cells/enzymology , Th17 Cells/immunology , Th17 Cells/metabolism
3.
Immunol Lett ; 233: 31-41, 2021 05.
Article in English | MEDLINE | ID: mdl-33722553

ABSTRACT

Perfluoroctanesulfonate (PFOS) belongs to a larger family of compounds known as Per- and polyfluoroalkyl substances (PFAS). The strength of the carbon-fluorine bond makes PFOS extremely resistant to environmental degradation. Due to its persistent nature, research has been directed to elucidating possible health effects of PFOS on humans and laboratory animals. Here we have explored the effects of PFOS exposure on immune development and function in mice. We exposed adult mice to 3 and 1.5 µg/kg/day of PFOS for 2 and 4 weeks, respectively, and examined the effects of PFOS exposure on populations of T cells, B cells, and granulocytes. These doses of PFOS resulted in serum levels of approximately 100 ng/mL with no weight loss during exposure. We find that PFOS does not affect T-cell development during this time. However, while PFOS exposure reduced immune cell populations in some organs, it also led to an increase in the numbers of cells in others, suggesting possible relocalization of cells. We also examined the effect of PFOS on the response to influenza virus infection. We find that exposure to PFOS at 1.5 µg/kg/day of PFOS for 4 weeks does not affect weight loss or survival, nor is viral clearance affected. Analysis of antibody and T cell specific antiviral responses indicate that at this concentration, PFOS does not suppress the immune cell development or antigen specific immune response.


Subject(s)
Alkanesulfonic Acids/pharmacology , Cell Differentiation/drug effects , Fluorocarbons/pharmacology , Granulocytes/drug effects , Granulocytes/immunology , Immunologic Factors/pharmacology , Lymphocytes/drug effects , Lymphocytes/immunology , Animals , Antibodies, Viral/blood , Antibodies, Viral/immunology , Biomarkers , Bone Marrow/drug effects , Bone Marrow/immunology , Bone Marrow/metabolism , Cell Differentiation/immunology , Female , Granulocytes/cytology , Granulocytes/metabolism , Immunophenotyping , Influenza A virus/immunology , Lymphocytes/cytology , Lymphocytes/metabolism , Male , Mice , Organ Specificity , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/metabolism , Orthomyxoviridae Infections/virology , Spleen/cytology , Spleen/drug effects , Spleen/immunology , Spleen/metabolism , Thymus Gland/immunology , Thymus Gland/metabolism
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