title: Screening Immunomodulators To Skew the Antigen-Specific Autoimmune Response.
abstract: Current therapies to treat autoimmune diseases often result in side effects such as nonspecific immunosuppression. Therapies that can induce antigen-specific immune tolerance provide an opportunity to reverse autoimmunity and mitigate the risks associated with global immunosuppression. In an effort to induce antigen-specific immune tolerance, co-administration of immunomodulators with autoantigens has been investigated in an effort to reprogram autoimmunity. To date, identifying immunomodulators that may skew the antigen-specific immune response has been ad hoc at best. To address this need, we utilized splenocytes obtained from mice with experimental autoimmune encephalomyelitis (EAE) in order to determine if certain immunomodulators may induce markers of immune tolerance following antigen rechallenge. Of the immunomodulatory compounds investigated, only dexamethasone modified the antigen-specific immune response by skewing the cytokine response and decreasing T-cell populations at a concentration corresponding to a relevant in vivo dose. Thus, antigen-educated EAE splenocytes provide an ex vivo screen for investigating compounds capable of skewing the antigen-specific immune response, and this approach could be extrapolated to antigen-educated cells from other diseases or human tissues.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kansas , Lawrence, Kansas 66047, United States.
authors.forename: Laura
authors.identifier: 0000-0003-1216-1998
authors.initials: L
authors.lastname: Northrup
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kansas , Lawrence, Kansas 66047, United States.
authors.forename: Bradley P
authors.initials: BP
authors.lastname: Sullivan
authors.affiliation: Bioengineering Graduate Program, University of Kansas , Lawrence, Kansas 66045, United States.
authors.forename: Brittany L
authors.initials: BL
authors.lastname: Hartwell
authors.affiliation: Department of Chemical and Petroleum Engineering, University of Kansas , Lawrence, Kansas 66045, United States.
authors.forename: Aaron
authors.initials: A
authors.lastname: Garza
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kansas , Lawrence, Kansas 66047, United States.|Bioengineering Graduate Program, University of Kansas , Lawrence, Kansas 66045, United States.|Department of Chemical and Petroleum Engineering, University of Kansas , Lawrence, Kansas 66045, United States.
authors.forename: Cory
authors.identifier: 0000-0002-9346-938X
authors.initials: C
authors.lastname: Berkland
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D005260:Female; D007108:Immune Tolerance / Q000276:immunology; D007155:Immunologic Factors / Q000276:immunology*; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D001324:Autoantigens; D016207:Cytokines; D007155:Immunologic Factors
keywords: EAE; antigen-specific; autoimmune; immunomodulators; screening; splenocytes; tolerance; tolerogenic adjuvants