Autoimmune Disease

Autoimmune Disease

The National Institutes of Health estimate that more than 23 million Americans suffer from autoimmune disease, making it one of the most prevalent categories of disease, ahead of both disease and cancer.


The immune system is a finely engineered defense system designed to shield our body from harmful pathogens and cancer cells. But sometimes the battle gets out of hand and the immune system turns on the very “self” it is meant to protect. What results are chronic autoimmune and inflammatory conditions that, over time, lead to tissue damage.

Investigators have catalogued over 80 such conditions: prominent among them are type 1 diabetes, in which immune cells destroy insulin-producing pancreatic cells, rheumatoid arthritis (RA), which attacks the lining of joints, and multiple sclerosis (MS), which irreparably damages the myelin sheath that covers nerve fibers. Related conditions include pathologies that don’t seem intuitively “autoimmune,” such as heart disease or Alzheimer’s, both of which have an inflammatory component.

Autoimmune Disease on the Rise

For reasons not yet understood, the incidence of autoimmune diseases is increasing in developed countries. Some attribute this surge to environmental toxins that incite an immune attack, and others to the obesity pandemic, as adipose tissue generates inflammatory factors. Others say it stems from exposure to bacterial or viral pathogens that induce a “mimicry response”, in which the body mistakes its own healthy cells for infected ones.

Whatever the cause, inappropriate mobilization of T cells against a person’s own tissues occurs in almost all autoimmunity. The good news is that a familiar cast of immune cell players often drives or repels the attack, meaning that drugs aimed at the pro-inflammatory contingent can sometimes be effective against multiple conditions. Among the most familiar are corticosteroids, wonder drugs first used 50 years ago to treat rheumatoid arthritis (RA) and now found in ointment form in most medicine cabinets.

Steroids have brought relief to sufferers of autoimmune conditions (and also saved lives of transplant patients) but their side effects limit long-term use. For patients with life-long autoimmune disease, non-steroidal treatments are now an option, thanks in part to what we’ve learned after almost three decades of research, some conducted at LJI, about signaling factors known as tumor necrosis factor (TNF) proteins.

New TNF blockers
TNF proteins, or “pro-inflammatory cytokines”, foment beneficial and harmful immune attacks by summoning lymphocytes to an inflammatory site and activating inflammation-related gene expression. Drugs blocking those signals, called TNF inhibitors, are now routinely used to treat RA and inflammatory bowel disease (IBD), but not all patients respond to them. For those individuals, LJI scientists are researching new ways to target TNF and even devising next-generation drugs to disrupt parallel anti-inflammatory pathways. Among the former, potential therapies emerging at LJI include novel anti-TNF drugs to treat two prominent IBDs: Crohn’s disease and ulcerative colitis, and the skin disease psoriasis, all of which are in clinical trials.

Among alternate strategies, LJI investigators are creating reagents to block activity of protein kinase C theta (PKCθ), an enzyme first discovered by LJI scientist, Amnon Altman, Ph.D., in the mid-90’s. PKCθ activates T cells, prompting drug companies to develop pharmaceuticals to block its catalytic activity to treat autoimmune conditions. However, given that PKCθ also has anti-infection activity, LJI scientists are taking a different tack by exploring ways to disrupt PKCθ interaction with a receptor expressed on T-cells. That strategy could block a destructive autoimmune response without compromising the body’s ability to fight infections.

LJI biologists also study structural proteins called septins, which form a molecular scaffold or cage around calcium channels that stud the surface of T cells. Opening of those channels is necessary to activate T cells, and LJI investigators have evidence that septins coordinate that activity. If so, that suggests that septins themselves could be targeted to dampen T cell activity when the immune system becomes overactive.


Amnon Altman, Ph.D.
Hilde Cheroutre, Ph.D.
Michael Croft, Ph.D.
Catherine “Lynn” Hedrick, Ph.D.
Matthias von Herrath, M.D.
Patrick Hogan, Ph.D.
Toshiaki Kawakami, M.D., Ph.D.
Mitchell Kronenberg, Ph.D.
Klaus Ley, M.D.
Anjana Rao, Ph.D.
Alessandro Sette, Dr. Biol.Sci.

From The Lab

Dec 12, 2018 // Expertscape

LJI Professor named world’s leading Type 1 Diabetes expert

The ranking was announced by Expertscape, an online knowledge base of worldwide biomedical expertise in many medical conditions, including type 1 diabetes
Oct 31, 2018 // Nature Communications, Cell Reports

LJI investigators discover how protein pair controls cellular calcium signals

Protein structure studies lay initial groundwork for novel treatments for immune cell dysfunction
Mar 23, 2018 // Science Immunology

Bystander T cells can steal the show from "professional" regulatory cells in resolving inflammation

LJI researchers show that non-specific bystander T cells can play an active role in countering type 1 diabetes
Jan 23, 2018

Groundbreaking Parkinson’s research at La Jolla Institute funded by Michael J. Fox Foundation

The two-year grant will focus on exploring the contribution of autoimmunity to Parkinson’s disease, providing new directions for therapy
Dec 26, 2017 // Cell Reports

LJI researchers report how T cells navigate the rough-and-tumble environment of the bloodstream

Study suggests ways to manipulate T cell migration in autoimmune or inflammatory disease