NEW INFORMATION ON THE DIFFERENCES BETWEEN Th1/Th17 AND Th2/Th9 CELLS IN THEIR MIGRATION INTO EYE TISSUES Data collected in this study (initiated and detailed in previous Annual Reports, mostly in FY 2015) were summarized in a manuscript submitted to Experimental Eye Research. Reviewers comments requested additional information on two issues: (i) The effect of the conjunctival inflammation in recipients of Th2/Th9 cells on goblet cells in this tissue. These cells were identified by staining with PAS. Unlike the typical increase in goblet cell number (hyperplasia) in classical allergic conjunctivitis, the number of goblet cells did not change in conjunctivae of mice with allergy-like reaction induced by Th2 cells. (ii) Measuring the proportion of eosinophils among the inflammatory cells in the recipient conjunctivae revealed the presence of eosinophils throughout the affected tissue, reaching up to 50% in areas in which eosinophils were aggregated. NEW INFORMATION CONCERNING THE IMMUNOMODULATING AGENT TMP778 Data collected in this study, detailed in previous Annual Reports, were summarized and submitted in a manuscript to the European Journal of Immunology. To address reviewers comments, we analyzed the eye infiltrating cells in mice treated with TMP778 or the vehicle control. The method we employed was intracellular flow cytometry and the collected data revealed that (i) the proportions of positive cells among total CD4 cells was approximately twice larger than the proportions found among CD4 cells in the spleen of the tested mice; (ii) similar to observations in the spleen, the proportion of infiltrating cells expressing interferon-gamma (IFN-g) was larger than of cells expressing interleukin (IL)-17 (This finding is of interest, since TMP778 is a selective inhibitor of RORgt, the transcription factor for IL-17.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAEY000069-40
Application #
9555659
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
40
Fiscal Year
2017
Total Cost
Indirect Cost
Name
U.S. National Eye Institute
Department
Type
DUNS #
City
State
Country
Zip Code
Tan, Cuiyan; Wandu, Wambui S; Lee, R Steven et al. (2017) Shedding New Light on the Process of ""Licensing"" for Pathogenicity by Th Lymphocytes. J Immunol 198:681-690
Canna, Scott W; Shi, Guangpu; Gery, Igal et al. (2017) Chronic, Systemic Interleukin-18 Does Not Promote Macular Degeneration or Choroidal Neovascularization. Invest Ophthalmol Vis Sci 58:1764-1765
Hinshaw, Samuel J H; Ogbeifun, Osato; Wandu, Wambui S et al. (2016) Digoxin Inhibits Induction of Experimental Autoimmune Uveitis in Mice, but Causes Severe Retinal Degeneration. Invest Ophthalmol Vis Sci 57:1441-7
Richard, Arianne C; Tan, Cuiyan; Hawley, Eric T et al. (2015) The TNF-family ligand TL1A and its receptor DR3 promote T cell-mediated allergic immunopathology by enhancing differentiation and pathogenicity of IL-9-producing T cells. J Immunol 194:3567-82
Richard, Arianne C; Tan, Cuiyan; Hawley, Eric T et al. (2015) Correction: The TNF-Family Ligand TL1A and Its Receptor DR3 Promote T Cell-Mediated Allergic Immunopathology by Enhancing Differentiation and Pathogenicity of IL-9-Producing T Cells. J Immunol 195:5839-40
Wandu, Wambui S; Tan, Cuiyan; Ogbeifun, Osato et al. (2015) Leucine-Rich Repeat Kinase 2 (Lrrk2) Deficiency Diminishes the Development of Experimental Autoimmune Uveitis (EAU) and the Adaptive Immune Response. PLoS One 10:e0128906
Tan, Cuiyan; Wei, Lai; Vistica, Barbara P et al. (2014) Phenotypes of Th lineages generated by the commonly used activation with anti-CD3/CD28 antibodies differ from those generated by the physiological activation with the specific antigen. Cell Mol Immunol 11:305-13
Zhao, Chan; Shi, Guangpu; Vistica, Barbara P et al. (2014) Induced regulatory T-cells (iTregs) generated by activation with anti-CD3/CD28 antibodies differ from those generated by the physiological-like activation with antigen/APC. Cell Immunol 290:179-84
Nugent, Lindsey F; Shi, Guangpu; Vistica, Barbara P et al. (2013) ITE, a novel endogenous nontoxic aryl hydrocarbon receptor ligand, efficiently suppresses EAU and T-cell-mediated immunity. Invest Ophthalmol Vis Sci 54:7463-9
Shi, Guangpu; Vistica, Barbara P; Nugent, Lindsey F et al. (2013) Differential involvement of Th1 and Th17 in pathogenic autoimmune processes triggered by different TLR ligands. J Immunol 191:415-23

Showing the most recent 10 out of 21 publications