Emil R. Unanue, M.D.

Professor
Pathology and Immunology

Immunology Program

  • 314-362-7440

  • 314-362-7444

  • 314-362-9108

  • 8118

  • BJCIH building 8th floor, Suite C, room 8414

  • unanue@wustl.edu

  • http://pathology.wustl.edu/faculty/index.php?user=831&pageload=indi

  • Immunology, autoimmunity, autoimmune diabetes, antigen presentation

  • We examine basic immunology of autoimmune diabetes focusing on T cell biology

Research Abstract:

The long-term goal of the laboratory is to understand antigen presentation, both at the cellular and biochemical level, and to correlate antigen presentation events to the response of CD4 T lymphocytes. Our current focus is entirely on autoimmune diabetes, examining the non-obese diabetic (NOD) mouse. We combine biochemical and biological parameters related to antigen selection, recognition and processing by antigen presenting cells (APC) and T cell selection. Our goals are to identify the initial cellular and molecular events that initiate and perpetuate this autoimmune disease.
Our investigations focus mostly on examining pancreatic islets at the early start of the diabetic process- we do this by isolating islets and examining the resident myeloid cells, the endothelial and mesenchymal cells, as well as the first entering T cells. Islets are mini-organs where the initiating events and interactions among cells can be examined in great detail. Cells can be isolated and examined by different functional and gene expression signatures. In the NOD mouse, diabetogenesis is already evident by the third week of life. Islets normally have a population of macrophages that is distinct from those that inhabit the exocrine pancreas.These macrophages have been extensively analyzed by us since they are vital for islet homeostasis and in the case of NOD, in the initiation of diabetes. The autoimmune process starts in islets with the entrance of CD4+ T cells and a small number of dendritic cells many of which are DC1 expressing the XCR1 protein. Many of the early T cells react to insulin peptides. We have extensively examined the insulin reactive T cells and characterized the insulin epitopes that are recognized by them. We examine how insulin peptides are presented to these insulin T cells, the role of the unique MHC class II molecules of the NOD [I-Ag7] and the various cellular interactions.
We are always looking for talented graduate students and post-docs interested in studying the nuances of autoimmune diabetes disease initiation

Selected Publications:

Selected Publications:

1. Xiaoxiao Wan, Bernd H. Zinselmeyer, Pavel N. Zakharov, Anthony N. Vomund, Ruth Taniguchi, Laura Santambrogio, Mark S. Anderson, Cheryl F. Lichti & Emil R. Unanue. Pancreatic islets communicate with lymphoid tissues via exocytosis of insulin peptides, Nature , 2018, in press, 10.1038/s41586-018-0341-6

2. Zinselmeyer BH, Vomund AT, Saundrs B, Johnson M, Carrero JA, UnanueER The resident pancreatic macrophages in pancreatic islets are constantly probing their local environment capturing beta cell granules and microparticles. Diabetologia, 2018, 61: 1374-1383

3. Carrero JA, McCarthy DP, Ferris ST, Wan X, Hu H, Zinselmeyer BH, Vomund AN, Unanue ER. Resident macrophages of pancreatic islets have a seminal role in the initiation of autoimmune diabetes of NOD mice. Proc Natl Acad Sci U S A. 2017 ;114: E10418-E10427. 29133429

4. Wan X, Thomas JW, Unanue ER: Class-switched anti-insulin antibodies originate from unconventional antigen presentation in multiple lymphoid sites. J Exp Med 2016:213: 967-978. PMCID27139492.
5. Calderon B, Carrero JA, Ferris ST, Sojka DK, Moore L, Epelman S, Murphy KM, Yokoyama WM, Randolph GJ, Unanue ER. The pancreas anatomy conditions the origin and properties of resident macrophages. J Exp Med. 2015 Sep 21;212(10):1497-512. PMC 4577842.

6. Vomund AN, Zinselmeyer BH, Hughes J, Calderon B, Valderrama C, Ferris ST, Wan X, Kanekura K, Carrero JA, Urano F, Unanue ER. Beta cells transfer vesicles containing insulin to phagocytes for presentation to T cells. Proc Natl Acad Sci U S A. 2015;112(40):E5496-502. PMC4603448.

7. Ferris ST, Carrero JA, Mohan JF, Calderon B, Murphy KM, Unanue ER. A minor subset of Batf3-dependent antigen-presenting cells in islets of Langerhans is essential for the development of autoimmune diabetes. Immunity. 2014 41 :657-69. PMC4220295.

8. Unanue ER. Antigen presentation in the autoimmune diabetes of the NOD mouse. Annu Rev Immunol. 2014;32:579-608. PubMed PMID: 24499272.

9. Mohan JF, Petzold SJ, Unanue ER. Register shifting of an insulin peptide-MHC complex allows diabetogenic T cells to escape thymic deletion. J Exp Med. 2011 ;208(12):2375-83. PMC3256971.

10. Mohan JF, Levisetti MG, Calderon B, Herzog JW, Petzold SJ, Unanue ER. Unique autoreactive T cells recognize insulin peptides generated within the islets of Langerhans in autoimmune diabetes. Nat Immunol. 2010 11:350-4. PMC3080751.

Last Updated: 7/27/2018 11:04:39 AM

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