Jared H. Rowe

     E-mail: rowe0100@umn.edu

     Year Entered: 2007

     Degrees Received:
     University of Minnesota
     Genetics, Cell Biology and Development
     B.S., 2007

     Honors and Awards:
     -NIH/NIDDK National Research Service Award for Individual
     Predoctoral MD/PhD Fellows, 2009-2014
     -Minnesota Medical Foundation's J. Jacob Kaplan Research Award
     and Beatrice Z. Milne and Theodore Brandenburg Research Award,
     2012
     -Microbiology, Immunology and Cancer Biology Graduate Program's
     Dr. Marvin and Hadassah Bacaner Research Award, 2012

     Thesis Advisor:   SingSing Way, M.D., Ph.D.

Thesis Research: The role of regulatory T cells during conditions of chronic and acute infections.

Pregnancy represents a unique physiologic state requiring the maternal immune sytem to simultaneously maintain host defense and tolerance to foreign antigens carried by the fetus. Although pregnancy confers unique susceptibility to infection, the pregnancy-associated immune defects that erode host defense remain largely undefined. We found that expansion of immune-suppressive Foxp3(+) regulatory T cells (Tregs), which occurs physiologically during pregnancy enhanced susceptibility to prenatal pathogens including Listeria and Salmonella species. Reciprocally, infection susceptibility was uniformly reduced with the selective ablation of Treg cells. Importantly however, the sustained expansion of maternal Tregs was essential for maintaining immune tolerance to the developing fetus because even partial transient ablation of Foxp3-expressing cells fractured maternal tolerance to fetal antigen and triggered fetal resorption. Interestingly, Foxp3 cell-intrinsic defects in the immune-suppressive cytokine IL-10 alone were sufficient to override Treg-mediated infection susceptibility, while IL-10 was nonessential for sustaining pregnancy. Thus, maternal Treg expansion required for sustaining pregnancy creates naturally occurring holes in host defense that confer prenatal infection susceptibility. These findings indicate that targeted therapeutics to protect pregnant women from serious infections can be generated via dissociating the basic biological mechanisms driving increased susceptibility to prenatal infections from those governing tolerance to the fetus.

Publications (pubmed):

Rowe JH, Ertelt JM, Xin L, Way SS. Pregnancy imprints regulatory memory that sustains anergy to fetal antigen. Nature. 2012 Oct 4;490(7418):102-6. 

Rowe JH, Ertelt JM, Xin L, Way SS. Listeria monocytogenes Cytoplasmic Entry Induces Fetal Wastage by Disrupting Maternal Foxp3(+) Regulatory T Cell-Sustained Fetal Tolerance. PLoS Pathog. 2012 Aug;8(8):e1002873.

Rowe JH, Ertelt JM, Way SS. Innate IFN-γ Is Essential for Programmed Death Ligand-1-Mediated T Cell Stimulation following Listeria monocytogenes Infection. J Immunol. 2012 Jul 15;189(2):876-84.

Ertelt JM, Johanns TM, Mysz MA, Nanton MR, Rowe JH, Aguilera MN, Way SS. Selective culling of high avidity antigen-specific CD4(+) T cells after virulent Salmonella infection. Immunology. 2011 Dec;134(4):487-97.

Ertelt JM, Rowe JH, Mysz MA, Singh C, Roychowdhury M, Aguilera MN, Way SS. Foxp3+ regulatory T cells impede the priming of protective CD8+ T cells. J Immunol. 2011 Sep 1;187(5):2569-77.

Rowe JH, Ertelt JM, Aguilera MN, Farrar MA, Way SS. Foxp3(+) Regulatory T Cell Expansion Required for Sustaining Pregnancy Compromises Host Defense against Prenatal Bacterial Pathogens. Cell Host Microbe. 2011 Jul 21;10(1):54-64

Johanns TM, Law CY, Kalekar LA, O'Donnell H, Ertelt JM, Rowe JH, Way SS. Early eradication of persistent Salmonella infection primes antibody-mediated protective immunity to recurrent infection. Microbes Infect. 2011 Apr;13(4):322-30.

Johanns TM, Ertelt JM, Rowe JH, Way SS. Regulatory T cell suppressive potency dictates the balance between bacterial proliferation and clearance during persistent Salmonella infection. PLoS Pathog. 2010 Aug 12;6(8). pii: e1001043.

Ertelt JM, Johanns TM, Rowe JH, Way SS. Interleukin (IL)-21-independent pathogen-specific CD8+ T-cell expansion, and IL-21-dependent suppression of CD4+ T-cell IL-17 production. Immunology. 2010 Oct;131(2):183-91.

Johanns TM, Ertelt JM, Lai JC, Rowe JH, Avant RA, Way SS. Naturally occurring altered peptide ligands control Salmonella-specific CD4+ T cell proliferation, IFN-gamma production, and protective potency. J Immunol. 2010 Jan 15;184(2):869-76.

Rowe JH, Johanns TM, Ertelt JM, Lai JC, Way SS. Cytotoxic T-lymphocyte antigen 4 blockade augments the T-cell response primed by attenuated Listeria monocytogenes resulting in more rapid clearance of virulent bacterial challenge. Immunology. 2009 Sep;128(1 Suppl):e471-8.

Ertelt JM, Rowe JH, Johanns TM, Lai JC, McLachlan JB, Way SS. Selective priming and expansion of antigen-specific Foxp3- CD4+ T cells during Listeria monocytogenes infection. J Immunol. 2009;182:3032-3038.

Rowe JH, Johanns TM, Ertelt JM, Way SS. PDL-1 blockade impedes T cell expansion and protective immunity primed by attentuate Listeria monocytes. J Immunol. 2008; 180:7553-7557.