Emil R. Unanue, M.D.

Pathology and Immunology

Immunology Program

  • 314-362-7440

  • 314-362-8752

  • 314-362-8748

  • 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, Listera immunity

  • 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 the autoimmune diabetes in the non-obese diabetic (NOD) mouse. We combine biochemical and biological parameters related to antigen selection, recognition and processing by antigen presenting cells (APC). We examine antigen presentation and the antigen presenting cells in the islets of Langerhans of the non-obese diabetic mouse. We want to identify the earliest events in autoimmunity in this confined tissue, and we believe the resident APCs are integral players in this early process. Islets normally have a population of macrophages that is distinct from those that inhabit the exocrine pancreas. In addition, the islets of the NOD mouse strain contain a minor population of dendritic cells (DC) that bear the CD103 integrin. We find close interactions between beta cells and the two APCs that result in the initiation of autoimmunity. Even under non-inflammatory conditions, beta cells transfer insulin-containing vesicles to the APCs of the islet. This reaction requires live cells and intimate contact. The autoimmune process starts in islets with the entrance of CD4+ T cells and an increase in the CD103+ DCs. Mice deficient in the Batf3 transcription factor never develop diabetes due to the absence of the CD103/CD8α lineage of DCs. We hypothesize that the 12-20 peptide of the beta chain of insulin is responsible for activation of the initial CD4+ T cell response during diabetogenesis. We are always looking for talented graduate students and post-docs interested in studying the nuances of autoimmune disease initiation.

Selected Publications:

1. 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. doi: 10.1084/jem.20150496. Epub 2015 Sep 7. PubMed PMID: 26347472; PubMed Central PMCID: PMC4577842.

2. 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 Oct 6;112(40):E5496-502. doi: 10.1073/pnas.1515954112. Epub 2015 Aug 31. PubMed PMID: 26324934; PubMed Central PMCID: PMC4603448.

3. 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 Oct 16;41(4):657-69. doi: 10.1016/j.immuni.2014.09.012. PubMed PMID: 25367577; PubMed Central PMCID: PMC4220295.

4. Unanue ER. Antigen presentation in the autoimmune diabetes of the NOD mouse. Annu Rev Immunol. 2014;32:579-608. doi: 10.1146/annurev-immunol-032712-095941. Epub 2014 Feb 5. Review. PubMed PMID: 24499272.

5. Calderon B, Carrero JA, Unanue ER. The central role of antigen presentation in islets of Langerhans in autoimmune diabetes. Curr Opin Immunol. 2014 Feb;26:32-40. doi: 10.1016/j.coi.2013.10.011. Epub 2013 Nov 16. Review. PubMed PMID: 24556398; PubMed Central PMCID: PMC4118295.

6. Carrero JA, Calderon B, Towfic F, Artyomov MN, Unanue ER. Defining the transcriptional and cellular landscape of type 1 diabetes in the NOD mouse. PLoS One. 2013;8(3):e59701. doi: 10.1371/journal.pone.0059701. Epub 2013 Mar 26.Erratum in: PLoS One. 2014;9(1). doi:10.1371/annotation/f277b29e-361b-4e56-b55b-612ebaca0432. PubMed PMID: 23555752; PubMed Central PMCID: PMC3608568.

7. 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 Nov 21;208(12):2375-83. doi: 10.1084/jem.20111502. Epub 2011 Nov 7. PubMed PMID: 22065673; PubMed Central PMCID: PMC3256971.

8. 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 Apr;11(4):350-4. doi:
10.1038/ni.1850. Epub 2010 Feb 28. PubMed PMID: 20190756; PubMed Central PMCID: PMC3080751.

Last Updated: 2/18/2016 2:05:26 PM

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