Inflammation

Inflammation

Heart disease and stroke, Alzheimer’s, type 2 diabetes, asthma, rheumatoid arthritis, multiple sclerosis and Chrohn’s disease. These seemingly unrelated conditions are united by a common characteristic: They are all fueled by chronic inflammation.

Overview

The medical media today is abuzz with warnings about “inflammation”. The word itself has become inflammatory and linked to almost every major health peril facing the developed world—from cancer and diabetes to heart disease and neurodegeneration—sending Americans racing to grocery stores to stock up on broccoli or pantry items required for a Mediterranean diet.

Those may be exactly what the doctor ordered. But what’s critical to remember, however, is that so is inflammation. It evolved as a good thing, a literal red alert that recruits rescuing immune cells to a site invaded by bacteria and viruses. And although its sequelae, such as swelling, fever, and fatigue, are often uncomfortable, acute inflammatory attacks are necessary for infections to pass and wounds to heal. Without them, no one would survive childhood.

The problem emerges when an inflammatory attack is not resolved and becomes chronic, as occurs in almost every inflammatory disease, including heart disease and stroke, type 2 diabetes, Parkinson’s Disease—or when it targets the wrong cells, as is the case in autoimmune conditions such as inflammatory bowel diseases (IBD).

Individual LJI scientists have made very significant strides against three inflammatory diseases in particular, namely coronary artery disease, lung disease and sickle cell disease. But in essence, whether they intend to or not, every LJI investigator works on inflammation. That’s because the same array of immune cell suspects often shows up in inflammatory, infectious and even allergic contexts.

Thus, given its deep history in understanding how organisms counter infection, LJI is well prepared to lead the charge against inflammatory disease, because often the same cells that rid us of infection are the ones that destroy healthy tissue in inflammatory or autoimmune disease.

Likewise, many of the same small molecules used by cells to signal to each other as they rout microbes are the ones that whip up unhealthy inflammatory responses, chief among them pro-inflammatory cytokines of the TNF family, which activate T cells and prolong their response. Several LJI faculty members have studied how these proteins work at the molecular level, and from their efforts have emerged TNF-inhibitors, some of the most widely used drugs to treat autoimmune disease.

Finally, an intriguing discovery of the last decade is that diseases like cancer have an inflammatory component. This revelation widens the immunology orbit even further and means that all immunologists not only work on inflammation, but also on cancer.

Illustrative of this serendipity is a discovery made in 2009 by LJI scientist Toshiaki Kawakami, M.D., PhD., who, while testing whether a particular enzyme might be acting to counter allergies (his area of expertise), engineered a mouse to lack that factor and found it, to his surprise, that it developed blood cancer. This accidental identification of a likely tumor suppressor gene illustrates the crosstalk ongoing at LJI and in labs worldwide, as scientists discover unexpected connections between inflammation and what were once considered unrelated diseases.

FACULTY MEMBERS

Hilde Cheroutre, Ph.D.
Michael Croft, Ph.D.
Catherine “Lynn” Hedrick, Ph.D.
Toshiaki Kawakami, M.D., Ph.D.
Klaus Ley, M.D.
Joel Linden, Ph.D.
Yun-Cai Liu, Ph.D.
Alessandro Sette, Dr. Biol.Sci.

From The Lab

Jul 26, 2017

No longer lost in translation

May 26, 2017 // LJI Lab rounds

TWEAKing Inflammation

Nov 13, 2016 // The San Diego Union Tribune

Our perpetually vigilant internal guardian

Nov 1, 2016

LJI scientists flip molecular switches to distinguish closely related immune cell populations

Aug 31, 2016

LJI researchers gain new understanding of how neutrophils latch onto vessel walls to protect from infection and clean up injured tissue