More than 50% of our immune system is located in the gut. The intestinal epithelium, which forms an interface between the organism and environment, is constitutively populated by intraepithelial lymphocytes (IEL) which are mostly T cells with an unique cellular composition and development compared to other T cells in the body. The IEL compartment comprises a variable mixture of conventional, MHC-restricted αβ T cells (predominantly CD8αβ+), and unconventional T cells such γδ T cells or αβ T cells expressing the CD8αα homodimer. Although IEL compose one of the largest T cell compartments in the body, a satisfactory understanding of IEL function and their interaction, and the consequence of such interaction, with the epithelial cells is still limited. This is problematic given that the IEL and the epithelial cells represent an important barrier in the prevention of infection against orally acquired pathogens and thus, are critical effector component of mucosal immunity. For many years, body surface epithelia was viewed to primarily contribute to host protection through its physicochemical barrier functions, however there is emerging evidence that epithelial cells are able to stimulate IEL and hence to regulate immune responses. This notwithstanding, few molecules used by epithelial cells to instruct immune cells in the intestine have been identified. The overall aim of our research is to characterize and understand the function of epithelial determinants that modulate immune responses of intestinal IEL and thus, to identify and explore novel IEL – epithelial cell interaction pathways. Our study focuses on novel immunoglobulin-like molecules, known as butyrophilin-like (Btnl) proteins, that are highly expressed by gut epithelial cells, and that by various criteria seem strong candidates for encoding novel immune regulators in the gut.
Our recent work has built on our observation that butyrophilin-like 1 (Btnl1), one of the Btnl family members, regulates functional interactions with intestinal T lymphocytes. With this as a basis to our work, my lab now focuses on establishing an improved understanding of the cross-talk between the Btnl-family members and the intestinal IEL under steady-state conditions as well as in relation to disease.
L. Boyden, J. Lewis, S. Barbee, A. Bas, M. Girardi, A. Hayday, R. Tigelaar, and R. Lifton. Skint1, the prototype of a newly identified immunoglobulin superfamily gene cluster, positively selects epidermal γδ T cells. Nature Genetics 2008; 40(5):656-62
Bas, A., Swamy, M., Abeler-Dörner, L., Williams, G., Pang, J., Barbee, S., and Hayday, A. Butyrophilin-like 1 encodes an enterocyte protein that selectively regulates functional interactions with T lymphocytes. Proc Natl Acad Sci USA 2011; 108(11): 4376-81.
Abeler-Dörner, L., Bas, A., Swamy, M., Clarke, S., and Hayday, A. A new experimental system identifies a novel functional collaboration between epithelial cells and intraepithelial lymphocytes. Manuscript under re-submission.
Abeler-Dörner L, Swamy M, Williams G, Hayday AC, Bas A. Butyrophilins: an emerging family of immune regulators. Trends Immunol. 2012 Jan; 33(1):34-41. Epub 2011 Oct 24.