BADERC- Howard Weiner

Howard Weiner, M.D.

Oral Autoantigens for the Treatment of Autoimmunity

Our laboratory has a long term interest in the modulation of autoimmune diseases by oral administration of autoantigens, and recently of aCD3. One of the models we have studied and are in the process of studying is the NOD model of diabetes. We have found that orally administered insulin can suppress or delay the onset of diabetes in these animals. We have also shown that the mechanism of action related to the generation of Th2 or Th3 type regulatory cells which suppress inflammation in the pancreatic islets. We continue our studies of animal models, trying to identify the effect of oral insulin in neonatal diabetes and ways in which to enhance the effect of the mucosally administered antigens. We have support for this work from the Juvenile Diabetes Association

References:

Karni A, Abraham M, Monsonego A, Cai G, Freeman GJ, Hafler D, Khoury SJ, Weiner HL. Innate immunity in multiple sclerosis: myeloid dendritic cells in secondary progressive multiple sclerosis are activated and drive a proinflammatory immune response. J Immunol. 2006 Sep 15;177(6):4196-202.
Gauthier SA, Glanz BI, Mandel M, Weiner HL. A model for the comprehensive investigation of a chronic autoimmune disease: the multiple sclerosis CLIMB study. Autoimmun Rev. 2006 Oct;5(8):532-6.
Faria AM, Weiner HL. Oral tolerance: therapeutic implications for autoimmune diseases. Clin & Dev Immunology 2006 Jun-Dec; 13 (2-4):143-57.
Carrier Y, Yuan J, Kuchroo VK, Weiner HL. Th3 Cells in Peripheral Tolerance. I. Induction of Foxp3-Positive Regulatory T Cells by Th3 Cells Derived from TGF-beta T Cell-Transgenic Mice. J Immunol. 2007 Jan 1;178(1):179-185.
Carrier Y, Yuan J, Kuchroo VK, Weiner HL.Th3 Cells in Peripheral Tolerance. II. TGF-beta-Transgenic Th3 Cells Rescue IL-2-Deficient Mice from Autoimmunity. J Immunol. 2007 Jan 1;178(1):172-178.
Gandhi R, Anderson DE, Weiner HL. Cutting Edge: Immature Human Dendritic Cells Express Latency-Associated Peptide and Inhibit T Cell Activation in a TGF-beta-Dependent Manner. J Immunol. 2007 Apr 1;178(7):4017-4021.
Ishikawa H, Ochi H, Chen ML, Frenkel D, Maron R, Weiner HL. Inhibition of autoimmune diabetes by oral administration of anti-CD3 monoclonal antibody. Diabetes. 2007 Aug;56(8):2103-9.
Awasthi A, Carrier Y, Peron JP, Bettelli E, Kamanaka M, Flavell RA, Kuchroo VK, Oukka M, Weiner HL.A dominant function for interleukin 27 in generating interleukin 10-producing anti-inflammatory T cells. Nat Immunol. 2007 Nov 11; [Epub ahead of print]
Abraham M, Karni A, Dembinsky A, Miller A, Gandhi R, Anderson D, Weiner HL. In vitro induction of regulatory T cells by anti-CD3 antibody in humans. J Autoimmun. 2008 Feb-Mar;30(1-2):21-8.
Sayegh MH, Weiner HL. Regulating rejection with cell therapy. Nat Biotechnol. 2008 Feb;26(2):191-2.
Basso AS, Frenkel D, Quintana FJ, Costa-Pinto FA, Petrovic-Stojkovic S, Puckett L, Monsonego A, Bar-Shir A, Engel Y, Gozin M, Weiner HL. Reversal of axonal loss and disability in a mouse model of progressive multiple sclerosis. J Clin Invest. 2008 Apr 1;118(4):1532-1543.
Quintana FJ, Basso AS, Iglesias AH, Korn T, Farez MF, Bettelli E, Caccamo M, Oukka M, Weiner HL. Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor.
Nature. 2008 Mar 23.
Vaknin-Dembinsky A, Brass S, Gandhi R, Weiner HL. Membrane bound IL-15 is increased on CD14 monocytes in early stages of MS. J Neuroimmunol. 2008 Mar 29.
Vaknin-Dembinsky A, Murugaiyan G, Hafler DA, Astier AL, Weiner HL. Increased IL-23 secretion and altered chemokine production by dendritic cells upon CD46 activation in patients with multiple sclerosis. J Neuroimmunol. 2008 Apr 8.
Chen ML, Yan BS, Bando Y, Kuchroo VK, Weiner HL. Latency-Associated Peptide Identifies a Novel CD4+CD25+ Regulatory T Cell Subset with TGF{beta}-Mediated Function and Enhanced Suppression of Experimental Autoimmune Encephalomyelitis. J Immunol. 2008 Jun 1;180(11):7327-37.






			Howard Weiner, M.D. Oral Autoantigens for the Treatment of Autoimmunity Our laboratory has a long term interest in the modulation of autoimmune diseases by oral administration of autoantigens, and recently of aCD3. One of the models we have studied and are in the process of studying is the NOD model of diabetes. We have found that orally administered insulin can suppress or delay the onset of diabetes in these animals. We have also shown that the mechanism of action related to the generation of Th2 or Th3 type regulatory cells which suppress inflammation in the pancreatic islets. We continue our studies of animal models, trying to identify the effect of oral insulin in neonatal diabetes and ways in which to enhance the effect of the mucosally administered antigens. We have support for this work from the Juvenile Diabetes Association References: Karni A, Abraham M, Monsonego A, Cai G, Freeman GJ, Hafler D, Khoury SJ, Weiner HL. Innate immunity in multiple sclerosis: myeloid dendritic cells in secondary progressive multiple sclerosis are activated and drive a proinflammatory immune response. J Immunol. 2006 Sep 15;177(6):4196-202. Gauthier SA, Glanz BI, Mandel M, Weiner HL. A model for the comprehensive investigation of a chronic autoimmune disease: the multiple sclerosis CLIMB study. Autoimmun Rev. 2006 Oct;5(8):532-6. Faria AM, Weiner HL. Oral tolerance: therapeutic implications for autoimmune diseases. Clin & Dev Immunology 2006 Jun-Dec; 13 (2-4):143-57. Carrier Y, Yuan J, Kuchroo VK, Weiner HL. Th3 Cells in Peripheral Tolerance. I. Induction of Foxp3-Positive Regulatory T Cells by Th3 Cells Derived from TGF-beta T Cell-Transgenic Mice. J Immunol. 2007 Jan 1;178(1):179-185. Carrier Y, Yuan J, Kuchroo VK, Weiner HL.Th3 Cells in Peripheral Tolerance. II. TGF-beta-Transgenic Th3 Cells Rescue IL-2-Deficient Mice from Autoimmunity. J Immunol. 2007 Jan 1;178(1):172-178. Gandhi R, Anderson DE, Weiner HL. Cutting Edge: Immature Human Dendritic Cells Express Latency-Associated Peptide and Inhibit T Cell Activation in a TGF-beta-Dependent Manner. J Immunol. 2007 Apr 1;178(7):4017-4021. Ishikawa H, Ochi H, Chen ML, Frenkel D, Maron R, Weiner HL. Inhibition of autoimmune diabetes by oral administration of anti-CD3 monoclonal antibody. Diabetes. 2007 Aug;56(8):2103-9. Awasthi A, Carrier Y, Peron JP, Bettelli E, Kamanaka M, Flavell RA, Kuchroo VK, Oukka M, Weiner HL.A dominant function for interleukin 27 in generating interleukin 10-producing anti-inflammatory T cells. Nat Immunol. 2007 Nov 11; [Epub ahead of print] Abraham M, Karni A, Dembinsky A, Miller A, Gandhi R, Anderson D, Weiner HL. In vitro induction of regulatory T cells by anti-CD3 antibody in humans. J Autoimmun. 2008 Feb-Mar;30(1-2):21-8. Sayegh MH, Weiner HL. Regulating rejection with cell therapy. Nat Biotechnol. 2008 Feb;26(2):191-2. Basso AS, Frenkel D, Quintana FJ, Costa-Pinto FA, Petrovic-Stojkovic S, Puckett L, Monsonego A, Bar-Shir A, Engel Y, Gozin M, Weiner HL. Reversal of axonal loss and disability in a mouse model of progressive multiple sclerosis. J Clin Invest. 2008 Apr 1;118(4):1532-1543. Quintana FJ, Basso AS, Iglesias AH, Korn T, Farez MF, Bettelli E, Caccamo M, Oukka M, Weiner HL. Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor. Nature. 2008 Mar 23. Vaknin-Dembinsky A, Brass S, Gandhi R, Weiner HL. Membrane bound IL-15 is increased on CD14 monocytes in early stages of MS. J Neuroimmunol. 2008 Mar 29. Vaknin-Dembinsky A, Murugaiyan G, Hafler DA, Astier AL, Weiner HL. Increased IL-23 secretion and altered chemokine production by dendritic cells upon CD46 activation in patients with multiple sclerosis. J Neuroimmunol. 2008 Apr 8. Chen ML, Yan BS, Bando Y, Kuchroo VK, Weiner HL. Latency-Associated Peptide Identifies a Novel CD4+CD25+ Regulatory T Cell Subset with TGF{beta}-Mediated Function and Enhanced Suppression of Experimental Autoimmune Encephalomyelitis. J Immunol. 2008 Jun 1;180(11):7327-37.