Daniel L. Mueller, M.D.
Director of Rheumatic and Autoimmune Diseases
Department of Medicine
University of Wisconsin - Madison, 1983, M.D.
612-625-8477 - office
612-625-8614 - lab
Dr. Daniel Mueller is a Professor of Medicine, and Director of Rheumatic and Autoimmune Diseases at the University of Minnesota Medical School. He undertook his medical studies at the University of Wisconsin-Madison School of Medicine, and later obtained his Internal Medicine training at the Ohio State University Hospital. In 1986, he received training in basic molecular immunology in the Laboratory of Immunology at the National Institute for Allergy and Infectious Disease, NIH, under Drs. Ronald Schwartz and William Paul. It is there that he initiated his research into fundamental mechanisms involved in the development and maintenance of immune self-tolerance. In 1990, Dr. Mueller entered the Rheumatology Training Program in the Rheumatic Diseases Division/Department of Internal Medicine at the University of Texas Southwestern Medical Center, under Dr. Peter Lipsky. Since the completion of his medical and research training, he has been on the University of Minnesota Medical School faculty. He is also a Director of the Autoimmunity Program, within the Medical School’s Center for Immunology. The major focus of his academic program is the investigation of the biological and biochemical mechanisms that underlie the maintenance of T- and B-cell tolerance within the peripheral immune system.
- T cell immune tolerance
- T cell clonal expansion
- Breakdown of B cell tolerance during autoimmune disease development
- Rheumatoid Arthritis
- Systemic Lupus Erythematosus
Current Research being conducted:
Autoimmunity develops as the consequence of a loss of tolerance to self-antigens. Investigations carried out by Dr. Daniel Mueller are leading to a better understanding of the biological and biochemical nature of immune self-tolerance. Of particular interest are those factors that determine whether prolonged and continuous antigen stimulation of a T-cell will lead to an increase in the clone size and the development of protective (or pathological) effector function, or lead to its functional inactivation (clonal anergy) and T-cell tolerance. Chronic antigen recognition in the absence of costimulatory ligands normally leads to clonal anergy induction, rather than aggressive immunity. This does not appear to be true, however, for individuals who are deficient in Foxp3+ T regulatory cells, where antigen recognition invariably leads to an expansion of the clone, continued functional responsiveness, and in some case immunopathology. Loss of T cell tolerance also leads to the expansion and differentiation of autoreactive B cells, and the development of B-dependent autoimmune disease. Currently, these biological principles are being investigated in models of CD4+ T cell-mediated immunopathology using both monoclonal KRN TCR-transgenic mice, as well as self antigen-specific polyclonal responder T cells from normal mice. Finally, translational experiments are underway that investigate the repertoire of human autoreactive B cells in normals as well as in patients with Rheumatoid Arthritis and Systemic Lupus Erythematosus.
Selected Recent Publications:
- Kalekar LA, Schmiel SE, Nandiwada SL, Lam WY, Barsness LO, Zhang N, Stritesky GL, Malhotra D, Pauken KE, Linehan JL, O'Sullivan MG, Fife BT, Hogquist KA, Jenkins MK, Mueller DL. 2016. CD4(+) T cell anergy prevents autoimmunity and generates regulatory T cell precursors. Nat Immunol. 17:304-14.
- Stritesky GL, Xing Y, Erickson JR, Kalekar LA, Wang X, Mueller DL, Jameson SC, and Hogquist KA. 2013. Murine thymic selection quantified using a novel method to capture deleted T cells. Proc. Natl. Acad. Sci. USA 110:4679-4684.
- Haasken S, Auger JL, Taylor JJ, Hobday PM, Goudy BD, Titcombe PJ, Mueller DL, and Binstadt BA. 2013. Macrophage scavenger receptor 1 (Msr1, SR-A) influences B cell autoimmunity by regulating soluble autoantigen concentration. J. Immunol. 191:1055-1062.
- Martinez RJ, Zhang N, Thomas SR, Nandiwada SL, Jenkins MK, Binstadt BA, and Mueller DL. 2012. Arthritogenic self-reactive CD4+ T cells acquire an FR4hiCD73hi anergic state in the presence of Foxp3+ regulatory T cells. J. Immunol. 188:170-181.
- Taylor JJ, Martinez RJ, Titcombe PJ, Barsness LO, Thomas, SR, Zhang N, Katzman SD, Jenkins MK and Mueller DL. 2012. Deletion and anergy of polyclonal B cells specific for ubiquitous membrane-bound self-antigen. J. Exp. Med. 209:2065-2077.
- Amin, S., Peterson, E., Reed, A.M., and Mueller, D.L. 2011. Pregnancy and Rheumatoid Arthritis: Insights into the Immunology of Fetal Tolerance and Control of Autoimmunity. Current Rheumatology Reports. Curr Rehematol Rep 13(5):449-55.
- Jenkins MK and Mueller DL. 2011. On the trail of arthritogenic T cells. Arthritis Rheum. 63:2851–2853.
- Mueller, D.L. 2010. Mechanisms maintaining peripheral tolerance. Nature Immunology 11:21-27.
- Agarwal P, Raghavan A, Nandiwada SL, Curtsinger JM, Bohjanen
PR, Mueller DL, Mescher MF. 2009. Gene regulation and chromatin
remodeling by IL-12 and type I IFN in programming for CD8
T cell effector function and memory. J.
Immunol. Aug 1;183(3):1695-704.
- Zhang R, Zhang N, Mueller DL.2008. Casitas B-lineage lymphoma
b inhibits antigen recognition and slows cell cycle progression
at late times during CD4+ T cell clonal expansion. J.
Immunol. Oct 15;181(8):5331-9.
- Obhrai JS, Oberbarnscheidt M, Zhang N, Mueller DL, Shlomchik
WD, Lakkis FG, Shlomchik MJ, Kaplan DH. 2008. Langerhans
Cells Are Not Required for Efficient Skin Graft Rejection. J.
Invest. Dermatol. Mar 13 (Epub).
- Yarke CA, Dalheimer SL, Zhang N, Catron DM, Jenkins MK,
and Mueller DL. 2008. Proliferating CD4+ T cells undergo
immediate growth arrest upon cessation of TCR signaling
in vivo. J.
- Richards DM, Zhang N, Dalheimer SL, and Mueller DL. 2007.
Allopeptide–specific CD4+ T cells help directly alloreactive
graft–infiltrating CD8+ T cells in the absence of
APC licensing. Am.
J. Transplant. 7:2269-2278.
- Mondino A, and Mueller DL. 2007. mTOR at the crossroads
of T cell proliferation and tolerance. Sem.
- Mueller DL. 2007. Molecular mechanisms supporting peripheral
T cell tolerance: Potential therapeutic approaches to autoimmunity
and allograft rejection. Sem.
- Nandiwada SL, Li W, Zhang R, and Mueller DL. 2006. p300/Cyclic
AMP-responsive element binding (CREB)-binding protein mediates
transcriptional co-activation by the CD28 T cell costimulatory
- Bonnevier JL, Yarke CA, and Mueller DL. 2006. Sustained
B7/CD28 interactions and resultant phosphatidylinositol
3-kinase activity maintain G1-->S phase transitions at
an optimal rate. Eur.
J. Immunol. 36:1583-1597.
- Vanasek, T.L., Nandiwada, S., Jenkins, M.K., and Mueller, D.L. 2006. CD25+ Foxp3+ regulatory T cells facilitate CD4+ T cell clonal anergy induction during the recovery from lymphopenia. The Journal of Immunology. 176:5880-5889.