Degrees and Certifications:
PhD

Rank and Title:
Professor Medicine

Department:
Departments of Internal Medicine,
Section of Rheumatology and Immunology/Microbiology

Endowed Professorship:

Office Location:
1735 W. Harrison St.
Cohn Building
7th Floor
Chicago, IL 60612

Laboratory Location:

Phone:
312-942-7847

Fax:
312-942-2808

E-mail:
alison_finnegan@rush.edu

Education:
PhD Immunology

Research Areas:
Animal Diseases
Biological Phenomena Cell Phenomena and Immunity
Biological Sciences
Genetic Processes
Immune System Diseases
Musculoskeletal Diseases

Laboratory Techniques:
Animal surgery/Modeling
Cytokine Assessment
ELISA Development
Flow Cytometry
PCR
Tissue Culture (Primary, Cell Line)
Transgenic Animal
Western Northern Southern Blotting

Hyperlinks:

Documents:

Faculty/Staff Description:
My laboratory investigates the cellular and molecule mechanism of several aspects of the immunopathogenesis of experimental autoimmune arthritis. In this model immunization with human proteoglycan (PG) in adjuvant induces a robust disease similar to rheumatoid arthritis PG-induced arthritis (PGIA) displaying many of the clinical, histolopathogical and immunolopathogical as well as genetic susceptibility and inheritance characteristics of human RA. PGIA develops in older female BALB/c and C3H mice and requires both T and B cells; autoantibodies or arthritic serum alone is not sufficient for the induction of arthritis.

PGIA is a Th-1-mediated disease regulated by several cytokines and transcription factors. Our studies in T cells are currently focused on the role of T cell cytokines and transcription factors in development of PGIA. CD4 T cells produce a robust IFNg response and IFNg is critically involved in the pathogenesis of PGIA. We utilize gene deficient mice to identify genes that control disease. We found that IL-12, STAT4, and IFNg are required for the development of disease. IL-12, STAT4, and IFNg are all classical cytokines and transcriptional factors that participate in Th-1 mediated responses. However, the transcription factor T-bet, which also belongs to the Th1-differentiation pathway, is not required for induction of arthritis. Our present studies involve understanding the role of T-bet in PGIA.

Th-1- responses in PGIA are regulated by IL-4. We have demonstrated that systemic administration of IL-4 effectively suppresses disease. We further showed that arthritis is exacerbated in IL-4^-/- mice and IL-4 mediates this effect through activation of STAT6. Aggravated arthritis in IL-4^-/- mice is associated with an increase in chemokine (MIP-1b, MIP-1a, MIP-2, and MCP-1) and cytokine (IL-12p35, IL-1b, IL-6, and TNF-a) transcripts in joints before development of any signs of inflammation or cellular infiltration. Thus, IL-4 may regulate the activation of resident synovial macrophages reducing infiltration of other leukocytes into the joint.

B cells are required for the development of PGIA. B cell depletion dramatically affects clinical symptoms in RA patients, this observation suggests that B cells are involved in the pathogenesis of the disease. B cell may perform multiple functions in the development of arthritis. Autoantibodies produced by B cells form immune complexes. These immune complexes can function through several different pathways to induce inflammation. Immune complexes bind to FcgR on macrophages and neutrophils activating proinflammatory chemokines and cytokines directing cells to sites of inflammation. Immune complexes can also activate the complement system. In PGIA, both FcgR and complement are involved in the development of disease. B cells may also function as antigen-presenting cells for T cell activation. Our current work is focus on costimulatory molecules and cytokines expressed by B cells and how they maintain T cell activation. Our overall hypothesis is that B cells are able to control the development of arthritis through stimulatory and inhibitory interactions that principally affect T cell activation. This is an important area of investigation, which is expected to shed new light on the mechanisms of B cell function in RA, and more generally in autoimmune disease, and thereby provide novel potential targets for the development of therapeutic strategies to selectively block or enhance immune responses.

O'Neill, S.K., Shlomchik, M.J., Glant, T.T., Cao, Y., Doodes, P.D., Finnegan, A. Antigen-specific B cells are required as APCs and autoantibody-producing cells for induction of severe autoimmune arthritis. J. Immunol. 174:3781-8, 2005.

Kaplan, C.D., Cao, Y., Verbeek, J.S., Tunyogi-Csapo, T, and Finnegan, A. Development of proteoglycan-inducedarthritis is critically dependent on Fcg receptor type III expression. Arthritis Rheum 52:1612-19, 2005.

Zhang, J., Bardos, T., Shao, Q., Tschopp, J., Mikecz, K., Glant, T.T., Finnegan, A. IL-4 potentiates activated T cell apoptosis via an IL-2-dependent mechanism. J. Immunol. 170:3495-503, 2003.

Finnegan, A., Grusby, M.J., Kaplan, C.D., O'Neill S.K, Eibel, H., Mikecz, K., and Zhang, J. IL-4 and IL-12 regulate proteoglycan-induced arthritis through Stat-dependent mechanisms. J. Immunol. 169:3345, 2002.

Selected Publications:

See CV