The Interface Between the Nervous and the Immune System in the Pathogenesis of Autoimmune Diabetes

Event Details

Meeting Objectives

The purpose of this workshop is to gain knowledge on the state-of-the-art and perspectives on the role of the central and peripheral nervous system on the pathogenesis and modulation of the inflammatory process that leads to selective beta cell destruction in type 1 diabetes (T1D) and also how the inflammatory process may affect neural control of islet cells function.

Background and Justification

T1D is thought to be caused by an immune system that has failed to maintain tolerance to self antigens expressed by the insulin-producing beta cell. For T1D, the currently known self antigens are mainly expressed in beta cells and some are also present elsewhere in the body, including neuronal antigens. There is some evidence for functional interactions between the nervous system and the immune system but the connections between islet autoimmunity and nervous system function are not known. Thus, this workshop will help shed light on the role of the central and peripheral nervous system on the pathogenesis and modulation of the inflammatory process that leads to selective beta cell destruction in T1D and also how the inflammatory process may affect neural control of islet cells function. Elucidation of these mechanisms could open new avenues for biomarkers or therapeutics.

Research Goals and Objectives

To discuss the role of the central and peripheral nervous system on the pathogenesis and modulation of the inflammatory process that leads to selective beta cell destruction in T1D and determine the effect of inflammation on neural control of islet cells function. The main questions that would be addressed are the following:

1. Does autoimmunity target the islet efferent and afferent innervation, does it induce an islet neuropathy, and does it influence autoreactivity against β cells?
2. Are neurotransmiters/neuropeptides important for β cell function, neogenesis, or regeneration?
3. Do signals from the nervous system alter inflammation and insulin resistance?
4. Does islet inflammation modulate islet innervation and neural function?
5. What is the role of innervation in the defective counter-regulatory response that is seen in T1D?
6. Are there other examples of neural involvement in tissue targeting in autoimmunity that could illuminate pathogenesis in T1D?

Understanding the role of the central and peripheral nervous system in T1D pathogenesis is likely to provide crucial new insights into disease pathogenesis.

Organizing Committee

Co-Chairs

Alejandro Caicedo, Ph.D., University of Miami
Hans-Michael Dosch, M.D., Ph.D., University of Toronto
Gerald Taborsky, Jr., Ph.D., University of Washington

NIDDK

Beena Akolkar, Ph.D., NIDDK, NIH
Michael Appel, Ph.D., NIDDK, NIH
Guillermo Arreaza-Rubin, M.D., NIDDK, NIH
Lisa Spain, Ph.D., NIDDK, NIH

Agenda

June 15, 2011

7:30 a.m. - 8:00 a.m.

Registration

Introductory Lecture

8:00 a.m. - 8:30 a.m.

Histopathology of Type 1 Diabetes in Pancreata from Cadaveric Organ Donors Objectives
Matthias von Herrath, M.D., Ph.D.

Session A: Influence of the Nervous System on Immune Responses - Possible Implications for Autoimmune Diabetes

Chair: Hans-Michael Dosch, M.D., Ph.D.

8:30 a.m. - 9:00 a.m.

A Role for Sensory Nerves in Islet Immune Responses
Hans-Michael Dosch, M.D., Ph.D.

9:00 a.m. - 9:30 a.m.

Neurons: Major Negative Regulators of Activated T cells
Shohreh Issazadeh-Navikas, Ph.D.

9:30 a.m. - 10:00 a.m.

Glutamate as a Regulator of Adaptive Immunity
Ursula Grohmann, Ph.D.

10:00 a.m. - 10:15 a.m.

Break

10:15 a.m. - 10:45 a.m.

The Inflammatory Reflex
Kevin Tracey, M.D.

10:45 a.m. - 11:15 a.m.

Sympathetic-Immune Modulation and Autoimmunity: Lessons Learned from Autoimmune Arthritis
Denise Bellinger, Ph.D.

11:15 a.m. - 11:45 a.m.

Questions and Roundtable Discussion

11:45 a.m. - 12:45 p.m.

Lunch (on your own)

Session B: Neural Dysfunction in Diabetes

Chairs: Alejandro Caicedo, Ph.D. and Gerald Taborsky, Jr., Ph.D.

Introductory Lectures

12:45 p.m. - 1:15 p.m.

Neural Control of the Pancreatic Islet
Alejandro Caicedo, Ph.D.

1:15 p.m. - 1:45 p.m.

Serotoninergic Pathways and cell Proliferation/Regeneration
Michael German, M.D.

Session B1: Islet Neural Dysfunction in Diabetes: Role of Autoimmunity

Chair: Alejandro Caicedo, Ph.D.

1:45 p.m. - 2:15 p.m.

Peri-Islet Glia in Autoimmune Type 1 Diabetes
Hubert Tsui, Ph.D.

2:15 p.m. - 2:45 p.m.

Immune Mediated Loss of Islet Sympathetic Nerves and Impairment of Glucagon Secretion
Gerald Taborsky, Jr., Ph.D.

2:45 p.m. - 3:15 p.m.

Lymphocyte Autoimmune Response to Nervous System Elements in the Course of Type 1 Diabetes
Joan Verdaguer, M.D., Ph.D.

3:15 p.m. - 3:30 p.m.

Break

Session B2: Neural Dysfunction in Diabetes: Role of Insulin Deficiency and Hyperglycemia

Chair: Gerald Taborsky, Jr., Ph.D.

3:30 p.m. - 4:15 p.m.

Dysfunction of the Hypothalamic-Islet Axis in Diabetes
Robert Sherwin, M.D.

4:15 p.m. - 4:45 p.m.

Vagal Contribution to Metabolic Homeostasis in Humans
Karen Teff, Ph.D.

4:45 p.m. - 5:15 p.m.

Diabetes-induced Dysfunction of Ganglionic Neurotransmission
Ellis Cooper, Ph.D.

Final Discussion

5:15 p.m.

Therapeutic Implications

Possible Research Initiatives in This Field