|
|
Susan Jackman, Ph.D. Office: MEB 117A |
Research Summary
We have been studying an autoimmune response directed to the skin in mice which targets the epidermal cell antigens called Skn with the following two projects:
Immunoregulation of Skn-Directed Autoimmunity
Subject of the dissertation by Dr. Pam Staton (2001), currently in the Forensic Science Department, Marshall University
When an immune response is initiated, important regulatory decisions determine the kind of response to be activated, the intensity of the response, and its duration. The cells and tissues involved in the response communicate with each other by way of soluble proteins called cytokines. Disturbances in cell-to-cell interactions or communication are thought to contribute to inappropriate immune responses, including autoimmunity. Recently we have found that after inducing skin lesions in our mouse model of autoimmunity, we can suppress the autoimmune response by introducing spleen cells obtained from a “normal” mouse. The result is that the mice have significantly reduced lesion severity. We also found that control of autoimmunity is associated with expression of the cytokine, interleukin-7 (IL-7) and that IL-7 gene therapy can suppress the development of skin lesions. Our lab is continuing to address the molecular and cellular mechanisms driving this regulatory response.
Genetic Characterization of the Mouse Skn Genes
In collaboration with Dr. Donald Primerano (Marshall) and Dr. Elizabeth Bryda (University of Missouri)
Early lesions in our Skn autoimmune mouse model display some features representative of psoriasis while later autoimmune pathology is suggestive of scleroderma, two human skin-based autoimmune diseases. Current treatment for most autoimmune diseases is primarily aimed at reducing symptoms, due in part to lack of knowledge regarding disease-specific autoantigens and their functions. The long-term objective of this research is to clone the Skn genes (Skn 1 and Skn 2) with the purpose of understanding the role of Skn proteins in mechanisms underlying differentiation, development and growth as they relate to normal function and to dysregulation during autoimmune pathogenesis.
A second focus of interest in our lab has been the study of Streptococcus agalactiae, group B streptococcus (GBS), the primary agent associated with life-threatening bacterial infections in the neonatal period.
Group B Streptococcal Response to Interleukin-6
Subject of the dissertation by Dr. Jennifer Smith (2002), currently at Dartmouth Medical School, Lebanon, New Hampshire
Neonates with GBS sepsis have elevated plasma levels of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-a, interleukin (IL)-1b, and IL-6. Such increases in cytokine concentrations, particularly TNF-a and IL-6, are associated with high mortality rates in both infants and adults with sepsis. In defenses against pathogens, cytokines promote many of the functions of earliest type of immune response called innate immunity. Bacteria often develop strategies to resist innate immunity. Characterization of bacterial responses to the host’s cytokine milieu is a newly emerging field. In preliminary in vitro studies, we have found that IL-6 enhanced GBS growth at high, but physiologically relevant, concentrations and increased expression of a set of genes (heat shock genes), which have been associated with virulence in other bacterial species. Our long-term goal is to understand the etiology of the IL-6 interaction with GBS that contributes to pathogenicity. Investigating cytokine-induced stress responses in GBS will contribute to understanding how GBS manipulates host innate immunity for survival and virulence. A clearer picture of host-bacteria interactions will have a significant impact in identifying additional targets for therapeutic and preventative strategies for control of GBS infection and colonization.
Selected Publications
Staton, P.J., A.B. Carpenter and S.H. Jackman. 2006. IL-7 is a critical factor in modulating lesion development in Skn-directed autoimmunity, J. Immunol. 176:3978-3986.
Jackman, S.H., E.A. Boyse and E.H. Goldberg. 1992. Adoptive transfer of skin selective autoimmunity by Skn alloantigenic disparities. Proc. Natl. Acad. Sci. (USA). 89:11041-11045.
Jackman, S.H., S. Keerthy, G. Perry. 2002. Murine epidermal cell antigen (SKN)-directed autoimmunity induced by transfer of CD4+ T cells. Ann. Clin. Lab. Sci. 32:171-180.
Smith, J.M., R.H. Respess, D.G.Chaffin, and S.H. Jackman. 2001. Differences in the innate immunologic response to group B streptococcus between colonized and noncolonized women. Infect. Dis. Obstet. Gynecol. 9:125-132.
Smith, J.M., J.A. Rexroth, D.G. Chaffin, S.H. Jackman. 2002. Serotyping of group B streptococcus in a small community hospital: an analysis of distribution and site of isolation. Infect. Dis. Obstet. Gynecol. 10:165-169.
Staton P.J., Carpenter A.B. and S.H. Jackman. 2006. IL-7 Is a Critical Factor in Modulating Lesion Development in Skn-Directed Autoimmunity. J. Immunol. 176: 3978-3986.