How does the immune system sense and respond to changes at barrier sites?
…An immunologist and a cardiologist are kidnapped. The kidnappers threaten to shoot one of them, but promise to spare whoever has made the greater contribution to humanity. The cardiologist says, “Well, I’ve identified drugs that have saved the lives of millions of people.” Impressed, the kidnappers turn to the immunologist. “What have you done?” they ask. The immunologist says, “The thing is, the immune system is very complicated …” And the cardiologist says, “Just shoot me now.”From Ed Yong ‘Immunology is where intuition goes to die’ credited to Jessica Metcalf
Unfortunately, there is truth to this joke. Immunology is complicated. So what I have learned in the past few years?
- What is present within tissues is also what shapes the local immune response.
- Changes within tissues may not be reflected in the blood.
- Understanding the mechanisms of tissue homeostasis is key to developing better treatments.
- Animal models help understand biological mechanisms but are limited in modeling human disease.
Factors that shape pulmonary immunity
During my PhD, I investigated tissue-specific responses in the airways and lungs. Our team showed the impact of diet and age on allergies and how the microbiome could influence chronic lung diseases.
Broadening my understanding of what constitutes the tissue microenvironment in the lungs, during my postdoc work, I investigated how the extracellular matrix shaped immunity and studied tissue-resident memory cells and their contribution to allergic responses.
Self and self-defence in the skin
Later in my career, I wanted to investigate the mechanisms of tissue-specific immunity in humans. The skin was the perfect organ since it is an important barrier equipped with specialized immune sentinel cells and could be accessed easily for experiments.
Working exclusively with human samples, opened my eyes to the wonderful world of unconventional T cells. These included T cells that respond to lipids in the context of nonclassical MHC molecules. In the skin, damage by ultraviolet (UV) radiations can change skin lipids. I wanted to understand whether our immune system can detect these changes and their implications for the early detection and elimination of nascent tumor cells. Specifically, I examined the role of the nonclassical MHC molecule CD1a, which is highly expressed in Langerhans cells,the immune sentinel cells in the skin.