@article{adams_collins_williams_holmes_hess_atkins_scheidemantle_liu_lodge_johnson_et al._2024, title={Myeloid cell MHC I expression drives CD8+ T cell activation in nonalcoholic steatohepatitis}, volume={14}, ISSN={["1664-3224"]}, url={https://doi.org/10.3389/fimmu.2023.1302006}, DOI={10.3389/fimmu.2023.1302006}, abstractNote={Background & aimsActivated CD8+ T cells are elevated in Nonalcoholic steatohepatitis (NASH) and are important for driving fibrosis and inflammation. Despite this, mechanisms of CD8+ T cell activation in NASH are largely limited. Specific CD8+ T cell subsets may become activated through metabolic signals or cytokines. However, studies in NASH have not evaluated the impact of antigen presentation or the involvement of specific antigens. Therefore, we determined if activated CD8+ T cells are dependent on MHC class I expression in NASH to regulate fibrosis and inflammation.}, journal={FRONTIERS IN IMMUNOLOGY}, author={Adams, Victoria R. and Collins, Leonard B. and Williams, Taufika Islam and Holmes, Jennifer and Hess, Paul and Atkins, Hannah M. and Scheidemantle, Grace and Liu, Xiaojing and Lodge, Mareca and Johnson, Aaron J. and et al.}, editor={Williams, Taufika Islam and Collins, Leonard B. and Kennedy, ArionEditors}, year={2024}, month={Jan} } @article{lim_hwang_yazdimamaghani_atkins_hyun_shin_ramsey_raedler_mott_perou_et al._2023, title={High-dose paclitaxel and its combination with CSF1R inhibitor in polymeric micelles for chemoimmunotherapy of triple negative breast cancer}, volume={51}, ISSN={["1878-044X"]}, DOI={10.1016/j.nantod.2023.101884}, abstractNote={The presence of immunosuppressive immune cells in tumors is a significant barrier to the generation of therapeutic immune responses. Similarly, in vivo triple-negative breast cancer (TNBC) models often contain prevalent, immunosuppressive tumor-associated macrophages in the tumor microenvironment (TME), resulting in breast cancer initiation, invasion, and metastasis. Here, we test systemic chemoimmunotherapy using small-molecule agents, paclitaxel (PTX), and colony-stimulating factor 1 receptor (CSF1R) inhibitor, PLX3397, to enhance the adaptive T cell immunity against TNBCs in immunocompetent mouse TNBC models. We use high-capacity poly(2-oxazoline) (POx)-based polymeric micelles to greatly improve the solubility of insoluble PTX and PLX3397 and widen the therapeutic index of such drugs. The results demonstrate that high-dose PTX in POx, even as a single agent, exerts strong effects on TME and induces long-term immune memory. In addition, we demonstrate that the PTX and PLX3397 combination provides consistent therapeutic improvement across several TNBC models, resulting from the repolarization of the immunosuppressive TME and enhanced T cell immune response that suppress both the primary tumor growth and metastasis. Overall, the work emphasizes the benefit of drug reformulation and outlines potential translational path for both PTX and PTX with PLX3397 combination therapy using POx polymeric micelles for the treatment of TNBC.}, journal={NANO TODAY}, author={Lim, Chaemin and Hwang, Duhyeong and Yazdimamaghani, Mostafa and Atkins, Hannah Marie and Hyun, Hyesun and Shin, Yuseon and Ramsey, Jacob D. and Raedler, Patrick D. and Mott, Kevin R. and Perou, Charles M. and et al.}, year={2023}, month={Aug} } @article{lee_you_taylor-just_tisch_bartone_atkins_ralph_antoniak_bonner_2023, title={Role of the protease-activated receptor-2 (PAR2) in the exacerbation of house dust mite-induced murine allergic lung disease by multi-walled carbon nanotubes}, volume={20}, ISSN={["1743-8977"]}, DOI={10.1186/s12989-023-00538-6}, abstractNote={Abstract}, number={1}, journal={PARTICLE AND FIBRE TOXICOLOGY}, author={Lee, Ho Young and You, Dorothy J. J. and Taylor-Just, Alexia and Tisch, Logan J. and Bartone, Ryan D. and Atkins, Hannah M. and Ralph, Lauren M. and Antoniak, Silvio and Bonner, James C.}, year={2023}, month={Aug} } @article{osborne_clark_whitcomb_devlin_lanza_atkins_2023, title={Unique Presentations of Burkholderia gladioli Infections in Several Strains of Immunocompromised Mice}, volume={73}, ISSN={["1532-0820"]}, DOI={10.30802/AALAS-CM-23-000016}, abstractNote={ Four strains of experimentally naïve mice (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ [NSG], NOD.Cg-Rag1tm1Mom Il2rgtm1Wjl/SzJ[NRG], B6.129S(Cg)-Stat1tm1Dlv/J [STAT1−/−], and B6.129S7-Ifngr1tm1Agt/J [IFNγR−/−] housed in a barrier facility developedunusual and seemingly unrelated clinical signs. Young NSG/NRG mice (n = 49, mean age = 4 ± 0.4 mo) exhibited nonspecificclinical signs of moderate-to-severe lethargy, hunched posture, decreased body condition, and pallor. In contrast to the NSG/NRGmice, the STAT1−/− and IFNγR−/−mice (n = 5) developed large subcutaneous abscesses on the head and neck. These micewere euthanized, and samples were collected for culture. NSG/NRG mice had moderate-markedly enlarged livers (20 of49, 40%) and spleens (17 of 49, 35%). The livers contained multiple, variably-sized, tan regions throughout all lobes. Histologyrevealed necrotizing hepatitis (13 of 17, 77%), splenic and hepatic extramedullary hematopoiesis (17 of 17, 100%), glomerularhistiocytosis (6 of 17, 35%), and metritis (6 of 11, 55%) with perivascular inflammation, suggesting hematogenous spreadDifferentials for these lesions included mouse hepatitis virus, ectromelia virus, Pseudomonas aeruginosa, Salmonella spp.,and Clostridium piliforme. Burkholderia gladioli was cultured from liver lesions and subcutaneous abscesses and confirmedwith 16S ribosomal RNA sequencing. After completing systematic testing of the environment, failure of the water autoclavecycle was suspected as the cause of the outbreak. To address the situation, individually ventilated racks were sanitized andnew breeders were purchased; these actions dramatically reduced B. gladioli infections. The current literature contains fewreports of B. gladioli infections in immunocompromised mice, and its typical presentation is torticollis and rolling. B. gladioliinfection is a potential differential for subcutaneous abscesses, hepatitis, and splenomegaly in immunocompromised mice.Careful monitoring of sterilization techniques is essential to prevent such infections in a barrier facility. }, number={5}, journal={COMPARATIVE MEDICINE}, author={Osborne, Andrea J. and Clark, Sarah E. and Whitcomb, Tiffany and Devlin, Penny and Lanza, Matthew and Atkins, Hannah M.}, year={2023}, month={Oct}, pages={391–397} } @article{lee_you_taylor-just_linder_atkins_ralph_cruz_bonner_2022, title={Pulmonary exposure of mice to ammonium perfluoro(2-methyl-3-oxahexanoate) (GenX) suppresses the innate immune response to carbon black nanoparticles and stimulates lung cell proliferation}, ISSN={["1091-7691"]}, DOI={10.1080/08958378.2022.2086651}, abstractNote={Abstract Background Per- and polyfluoroalkyl substances (PFAS) have been associated with respiratory diseases in humans, yet the mechanisms through which PFAS cause susceptibility to inhaled agents is unknown. Herein, we investigated the effects of ammonium perfluoro(2-methyl-3-oxahexanoate) (GenX), an emerging PFAS, on the pulmonary immune response of mice to carbon black nanoparticles (CBNP). We hypothesized that pulmonary exposure to GenX would increase susceptibility to CBNP through suppression of innate immunity. Methods Male C57BL/6 mice were exposed to vehicle, 4 mg/kg CBNP, 10 mg/kg GenX, or CBNP and GenX by oropharyngeal aspiration. Bronchoalveolar lavage fluid (BALF) was collected at 1 and 14 days postexposure for cytokines and total protein. Lung tissue was harvested for histopathology, immunohistochemistry (Ki67 and phosphorylated (p)-STAT3), western blotting (p-STAT3 and p-NF-κB), and qRT-PCR for cytokine mRNAs. Results CBNP increased CXCL-1 and neutrophils in BALF at both time points evaluated. However, GenX/CBNP co-exposure reduced CBNP-induced CXCL-1 and neutrophils in BALF. Moreover, CXCL-1, CXCL-2 and IL-1β mRNAs were increased by CBNP in lung tissue but reduced by GenX. Western blotting showed that CBNP induced p-NF-κB in lung tissue, while the GenX/CBNP co-exposed group displayed decreased p-NF-κB. Furthermore, mice exposed to GenX or GenX/CBNP displayed increased numbers of BALF macrophages undergoing mitosis and increased Ki67 immunostaining. This was correlated with increased p-STAT3 by western blotting and immunohistochemistry in lung tissue from mice co-exposed to GenX/CBNP. Conclusions Pulmonary exposure to GenX suppressed CBNP-induced innate immune response in the lungs of mice yet promoted the proliferation of macrophages and lung epithelial cells.}, journal={INHALATION TOXICOLOGY}, author={Lee, Ho Young and You, Dorothy J. and Taylor-Just, Alexia J. and Linder, Keith E. and Atkins, Hannah M. and Ralph, Lauren M. and Cruz, Gabriela and Bonner, James C.}, year={2022}, month={Jun} }