Hui Zhi, Ph.D.

Can we harness the hidden powers of our own tissue-resident immune cells against viral infections?

FUNDED: JULY 2021
FUNDED BY: the generosity of James Isaacs

The COVID-19 pandemic underlines the urgent need to understand how our immune system protects us and find general treatments against viral infection. While antibodies and killer T cells circulating in the bloodstream have drawn the most attention for their powerful antiviral effect, there is an often overlooked but equally important part of the immune system: tissue-resident immune cells. Among them are so-called type 1 innate lymphoid cells (ILC1), which are among the first responders when a viral infection is trying to gain a foothold in the body. Due to the critical role of ILC1s, it is imperative to understand how ILC1s execute its protective function against viral infection.

In the Benedict laboratory, we have recently discovered that ILC1s can act like killer T cells, in that they can identify and destroy virus-infected cells. I want to identify and characterize the potent “weapons” ILC1s possess in their arsenal to better harness the hidden powers of ILC1s against viral infections. Most likely, ILC1s don’t use their full complement of weapons unless they encounter stressed cells, therefore I will use state of the art ‘omics’ techniques to thoroughly analyze the genes and proteins produced by ILC1 during virus infections, and identify the most powerful proteins ILC1s utilize to combat virus.

The identification of the protective function of ILC1s will deepen our understanding of how tissue-resident cells respond to emergencies and could help us better harness them for treating infectious diseases like COVID-19. Interestingly, ILCs also run constant immunosurveillance to spot and eradicate malignant cells before they can grow into a tumor. Thus a better understanding of the weapons ILC1s could also help inform new therapeutic strategies for cancers.

Six-Month Project Update

Type 1 innate lymphoid cells (ILC1) are among the first responders when a viral infection is trying to gain a foothold in the body. ILC1 cells reside in the tissues and run constant immunosurveillance to spot and eradicate any danger. My goal in this new study is to harness single-cell RNA sequencing techniques to identify the most powerful proteins ILC1 cells use to combat viruses.

Most likely, ILC1 cells don’t use their full complement of “weapons” unless they encounter stressed cells, possibly due to the constant expression of CD200R on these cells (an anti-inflammatory receptor that controls the activation of ILC1 cells). Therefore, in my experiments thus far, I’ve stimulated these cells by treating mice with either pro-inflammatory reagent or antibodies that block CD200R signaling, which did in turn further activate ILC1 cells. After these stimulations, liver and salivary gland ILC1 cells were purified and sent for single-cell RNA sequencing for further analysis. My next steps will be to analyze the sequencing data and identify effector proteins of ILC1 cells uniquely expressed under stimulation. From these data, we plan to further test which of those proteins are most powerful for treating viral infection and cancers.