The main focus of the lab is the role of T cells in the initiation of lacrimal and salivary gland autoimmunity characteristic of Sjögren syndrome. Through the use of animal models that spontaneously develop Sjögren syndrome–like autoimmunity of lacrimal and/or salivary glands, we are dissecting the pathogenic roles of CD4 and CD8 effector T cells as well as the role of regulatory T cell dysfunction in the initiation of organ-specific autoimmune manifestations. The nonobese diabetic (NOD) mouse and related strains spontaneously develop Sjögren syndrome–like autoimmunity affecting the lacrimal and salivary glands; however, in individual mice disease affects only either lacrimal or salivary glands based largely on poorly defined mechanisms driven by sex-specific factors. We have recently identified sex differences in organ-protective regulatory T cells in NOD mice, though specific mechanisms of their dysfunction remain to be determined. While the infiltrating T cells in both human biopsy specimens and animal models of Sjögren syndrome are invariably comprised of both CD8 and CD4 T cells, the specific requirements and contributions of each T cell subset are not understood. Similarly, the initial events responsible for the autoimmune attack on specific organs (while leaving other organs untouched) are not well defined. We have recently identified requisite roles for interleukin 27 and type I interferons in the development of Sjögren syndrome-like autoimmunity in NOD mice. Our current studies aim to define how these cytokines drive immune dysregulation resulting in autoimmunity. Ultimately, understanding these initial events in autoimmune disease development will allow us to identify novel targets for diagnostic and therapeutic modalities.

Our current projects include:

1. Defining the mechanisms by which interleukin 27 signaling drives pathogenic effector T cells to overcome regulatory mechanisms in the development of lacrimal and salivary gland autoimmunity in the NOD mouse model of Sjögren syndrome.

2. Identification of the mechanisms by which type I interferon signaling drives lacrimal gland autoimmunity in NOD mice.