Research


Regulation of adaptive immune responses by type 1 interferon


Our lab is generally interested in how a collective group of secreted proteins called cytokines, regulate adaptive immune responses to pathogens.  Our current focus is on a subclass of cytokines called type 1 interferon.  The first description of type 1 interferon was published in 1957, making it the very first immune cytokine discovered.  It was identified based on its activity to inhibit influenza virus replication.  Since then, scientists have learned a great deal about interferon’s anti-viral properties, and it is commonly used to treat humans for a variety of diseases such as hepatitis C and multiple sclerosis. 


Type 1 interferon is a class of related genes that code for a group of highly related secreted molecules that all bind a single interferon receptor.  Almost any cell in your body can secrete interferon if it becomes infected with certain viruses, and most all cells can respond to interferon due to the widespread expression of the receptor.  Even though interferon is a powerful anti-viral signal, viruses and other intracellular pathogens can still persist and cause devastating diseases if the adaptive arm of the immune system is not functioning properly.  Given that interferon is one of the very first lines of defense against viruses, very little is known about how interferon influences the adaptive immune system, and that is where our research is focussed.


The adaptive arm of the immune system consists basically of two cell types that fall into the lymphocyte category and are called B cells and T cells.  B cells are responsible for making antibody that neutralizes viruses and bacteria and provides protection against reinfection.   T cells serve many functions that range from helping B cells function to directly killing virally infected cells.  Recently, we have discovered two unique activities that type 1 interferon regulates in human T cells.  First we have found that, unlike other inflammatory cytokines, type 1 interferon promotes the development of a subclass of T cells that provide long-lived protection from re-infection.  These specialized T cells are called central memory T cells, and they are critical to the success of vaccines.  We have found that type 1 interferon is a potent factor that drives memory T cell expansion and activity, and you can read more about these findings in our recent publications. 


Secondly, we have recently discovered that type 1 interferon blocks the development of a subclass of T cells that cause allergy and asthma.  These T cells are called T helper type 2 (Th2) cells.  Allergy and asthma are related immune disorders that are mediated by T cells.  Under normal circumstances, the immune system ignores common environmental substances such as pollen, dust, exhaust, etc.,  However, for reasons that are not clear, T cells from some individuals become hyper-activated by these substances and attack the organ sites at which these substances are inhaled or contacted.  These T cells secrete large quantities of inflammatory cytokines that lead to rashes, sinus allergies, ulcers, and lung inflammation in the case of asthma.  By studying primary human T cells, we have found that type 1 interferon potently inhibits the development of Th2 cells, and importantly, interferon can inhibit the secretion of inflammatory cytokines from pre-committed Th2 cells.  Based on these findings, our ongoing studies will determine whether type 1 interferon could be a successful treatment for allergies and asthma.


Farrar Lab