Genetics of susceptibility to infectious and autoimmune disease
Dr. Teuscher received his Ph.D. in Pathology at the University of New Mexico in 1982. In 1984 he joined the faculty at the University f Pennsylvania School of Medicine. Dr. Teuscher returned to the Intermountain West as an Associate Professor of Microbiology at Brigham Young University. In 2001, following a stent at the University of Illinois Urbana-Champaign as a Professor of Veterinary Pathobiology, he moved to the University of Vermont where he is a Professor of Medicine and Pathology.
A co-evolutionary genetic link between susceptibility to infectious and autoimmune disease has long been suspected. In the molecular arms race between pathogens and host defense genes, polymorphism in genes controlling antigen-specific molecular interactions are considered the quintessential examples of infectious disease gene alleles that contribute to autoimmune disease susceptibility. However, it has been estimated that approximately half of the host genetic variability contributing to infectious disease resistance is a function of genes encoding for non-antigen specific molecules. Thus, the identification of polymorphic, non-antigen dependent molecules controlling susceptibility to infectious agents, or their products, and autoimmune disease would provide considerable insight into the nature of such genes.
With the advent of genome scanning technology and high resolution congenic mapping, a large number of infectious and autoimmune disease susceptibility loci have been mapped. Early on it became evident that several of these loci resided on the same chromosomes and colocalized within the same genetic intervals. We hypothesized that this phenomenon represented either single, shared disease susceptibility genes or members of gene complexes involved in multiple immunopathologically mediated phenotypes. This hypothesis has recently been validated when we identified Bphs, the locus controlling susceptibility to Bordetella pertussis induced hypersensitivity to histamine and autoimmune disease in mice, as the histamine H1 receptor. Mechanistically, Bphs/Hrh1 controls both the induction and effector phases of the disease process. Similar positional-candidate gene cloning approaches are underway to identify genes underlying previously mapped infectious and autoimmune disease QTL in the mouse.
Case LK, Huber SA, Teuscher C. Inheritance of coronary artery disease in men. Lancet. 2012 Jun 30;379(9835):2424-5
Saligrama N, Noubade R, Case LK, Del Rio R, Teuscher C. Combinatorial roles for histamine H(1) -H(2) and H(3) -H(4) receptors in autoimmune inflammatory disease of the central nervous system. Eur J Immunol. 2012 Jun;42(6):1536-46.
del Rio R, Noubade R, Saligrama N, Wall EH, Krementsov DN, Poynter ME, Zachary JF, Thurmond RL, Teuscher C. Histamine H4 receptor optimizes T regulatory cell frequency and facilitates anti-inflammatory responses within the central nervous system. J Immunol. 2012 Jan 15;188(2):541-7.
Lu C, Diehl SA, Noubade R, Ledoux J, Nelson MT, Spach K, Zachary JF, Blankenhorn EP, Teuscher C. Endothelial histamine H1 receptor signaling reduces blood-brain barrier permeability and susceptibility to autoimmune encephalomyelitis. Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):18967-72.
Teuscher C, Subramanian M, Noubade R, Gao JF, Offner H, Zachary JF, Blankenhorn EP. Central histamine H3 receptor signaling negatively regulates susceptibility to autoimmune inflammatory disease of the CNS. Proc Natl Acad Sci U S A. 2007 Jun 12;104(24):10146-51.
Spach KM, Noubade R, McElvany B, Hickey WF, Blankenhorn EP, Teuscher C. A single nucleotide polymorphism in Tyk2 controls susceptibility to experimental allergic encephalomyelitis. J Immunol. 2009 Jun 15;182(12):7776-83.
Teuscher C, Noubade R, Spach K, McElvany B, Bunn JY, Fillmore PD, Zachary JF, Blankenhorn EP. Evidence that the Y chromosome influences autoimmune disease in male and female mice. Proc Natl Acad Sci U S A. 2006 May 23;103(21):8024-9.
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