How does the immune system sense and respond to changes at barrier sites?

In short -it is complicated. My approach to this question is shaped by what I have learned across the breadth of my research experience.

  1. The context provided by the tissue microenvironment shapes the nature of an immune response locally. For instance, the same cytokine can generate a proinflammatory or an anti-inflammatory response depending on other factors in the microenvironment.
  2. Responses within tissues are not always reflected in the systemic compartment in circulation.
  3. Investigating basic mechanisms that help in the maintenance of health/homeostasis in tissues are pivotal to make new drug discoveries and develop new therapeutic strategies in disease.
  4. Preclinical models can be limiting in addressing issues of human health.

Factors that shape pulmonary immunity

During my doctoral work at the laboratory of Prof. Benjamin Marsland at the University of Lausanne, Switzerland, I investigated tissue-specific responses in the context of infectious and chronic lung diseases. We demonstrated the impact of diet and age on the pathogenesis of allergic asthma and how the microbiome can influence chronic lung diseases. I also discovered previously unknown functions for the epithelial-derived cytokine, TSLP, in mediating antiviral immunity and in the pathogenesis of non-atopic asthma.

Building upon this theme of tissue- resident immunity, during my postdoc work in the lab of Paul Bollyky, at Stanford University, I investigated how extracellular matrix shaped immunity and studied tissue-resident memory cells and their contribution to chronic lung diseases.

Self and self-defence in the skin

The skin is well adapted to deal with site specific stresses.

Although the immune system can detect and respond to foreign invaders (non-self), it is also continually monitoring changes within our tissues (self). In the skin, damage by ultraviolet (UV) radiations can change skin lipids. I investigated how our immune system can detect these changes and its implications in the early detection and elimination of nascent tumour cells. Specifically, I examined the role of CD1a, a protein which is highly expressed on the immune sentinel cells in the skin.