Shannon Dunn, DPhil, ARLAT, PhD

Multiple Sclerosis (MS) is an inflammatory disease characterized by recurrent episodes of immune-mediated attack of central nervous system myelin leading to axon damage and progressive disability. T helper cells specific to myelin antigens are thought to orchestrate the autoimmune attack in this disease. For reasons that are still unclear, women develop MS more frequently than men. The goal of our research is to understand the underlying reasons for the sex difference in the pattern of this disease. Research has indicated that upon exposure to antigen, T cells of female mice expand more rapidly and exhibit enhanced production of pro-inflammatory cytokines such as interferon gamma and interleukin 17 upon stimulation. Although this more robust T cell response may be beneficial to the clearance of unwanted pathogens, it is detrimental in the context of central nervous system inflammation in MS. Our current research is focused on defining how sex hormones may be responsible for modulating the activity of these auto-reactive T helper cells during experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis.

My current reserach interests are:
  • PPARalpha as a mediator of androgen effects on T cell autoimmunity
    We are interested in how male sex hormones act to limit the activity of auto-aggressive T cells in EAE. We have found that androgens suppress the production of pro-inflammatory cytokines by these cells. We have also made the discovery that the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha) is expressed at higher levels in male as compared to female T helper cells and that the expression of this molecule is sensitive to the levels of androgens. Our studies also indicate that the activity of PPARalpha controls the development of T helper 1 inflammation selectively in male mice during EAE. Our current research effort is directed towards understanding the mechanism of how this molecule and other PPAR molecules may limit the development of autoimmunity.
  • Biphasic effects of estrogen on EAE
    We are also interested in how female sex hormones may regulate the activity of autoaggressive T helper cells during EAE. Our preliminary work has indicated that this hormone can have both immune stimulatory and anti-inflammatory effects that appear to be dependent on the circulating levels of this hormone. It is well-documented that pregnancy levels of this hormone have profound effects in suppressing myelin-directed T cell responses during EAE. Our work has indicated that lower levels of this hormone (nM range) associated with the menstrual cycle in women or the diestrus stage in mice can enhance the formation of T helper 17 cells that are known to be pathogenic in MS and EAE. Future research will be directed towards defining the cellular and molecular basis of this biphasic effect of estrogen on the development of autoimmunity during EAE.
Proc Natl Acad Sci U S A. 2019 Nov 05;116(45):22710-22720
Cahill LS, Zhang MA, Ramaglia V, Whetstone H, Sabbagh MP, Yi TJ, Woo L, Przybycien TS, Moshkova M, Zhao FL, Rojas OL, Gomes J, Kuerten S, Gommerman JL, Sled JG, Dunn SE
J Immunol. 2019 Nov 15;203(10):2588-2601
Drohomyrecky PC, Doroshenko ER, Akkermann R, Moshkova M, Yi TJ, Zhao FL, Ahn JJ, McGaha TL, Pahan K, Dunn SE
Pain. 2018 Dec 11;:
Mifflin KA, Yousuf MS, Thorburn KC, Huang J, Pérez-Muñoz ME, Tenorio G, Walter J, Ballanyi K, Drohomyrecky PC, Dunn SE, Kerr BJ
J Immunol. 2018 Sep 26;:
Zhao FL, Ahn JJ, Chen E, Yi TJ, Stickle NH, Spaner D, Zúñiga-Pflücker JC, Dunn SE
Cell Metab. 2018 Aug 22;:
Tsai S, Clemente-Casares X, Zhou AC, Lei H, Ahn JJ, Chan YT, Choi O, Luck H, Woo M, Dunn SE, Engleman EG, Watts TH, Winer S, Winer DA
J Exp Med. 2018 May 17;:
Dunn SE, Ousman SS, Sobel RA, Zuniga L, Baranzini SE, Youssef S, Crowell A, Loh J, Oksenberg J, Steinman L
Bioorg Med Chem. 2017 Mar 06;:
Sarswat A, Wasilewski E, Chakka SK, Bello AM, Caprariello AV, Muthuramu CM, Stys PK, Dunn SE, Kotra LP
J Vis Exp. 2016 Nov 16;(117):
Ahn JJ, Selvanantham T, Zhang MA, Mallevaey T, Dunn SE
PLoS One. 2016;11(3):e0151224
Chruscinski A, Huang FY, Nguyen A, Lioe J, Tumiati LC, Kozuszko S, Tinckam KJ, Rao V, Dunn SE, Persinger MA, Levy GA, Ross HJ



Assistant Professor, Department of Immunology, University of Toronto