Role of IL-36 in Pustular Psoriasis and Its Female Skewing
Principal Investigator: Mrinal Sarkar, Ph.D.
Institution: University of Michigan
Grant Mechanism: Translational Research Grant
Funding Amount: $200,000
Project Start Date: August 1, 2021
Project End Date: July 30, 2023
Keywords: Immunology, Gene Expression, Psoriasis
Pustular psoriasis is a devastating subtype of psoriasis associated with significant morbidity and mortality. Pustular psoriasis is the only form of psoriasis that shows prominent sex bias with the majority of cases found in women. The cause of this sex bias in pustular psoriasis is unknown and has not been previously studied. The IL-36 family, consisting of three cytokines, IL-36A, IL-36B, and IL-36G, and their receptor antagonist (IL-36RA), has recently been shown to have an important role in psoriasis, particularly pustular psoriasis. Some genetic evidence also indicates that a few other molecules, such as CARD14, AP1S3, IL36RN, and SERPINA3 may be involved in pustular psoriasis by regulating IL-36. However, little is known about the function of each IL-36 member, their regulation, and the mechanisms behind the sex bias in IL-36 responses in pustular psoriasis. To investigate these, we are aiming to determine (1) the role of each IL-36 cytokine in pro-inflammatory responses in skin. (2) the dependence of pustular psoriasis-associated CARD14, AP1S3, IL36RN, and SERPINA3 mutations on IL-36 cytokines and IL-36 activation, (3) mechanisms behind sexually dimorphic responses to IL-36.
This grant was funded by the Dr. M. Alan Menter Translational Research Grant.
Mrinal Sarkar, Ph.D. joined the University of Michigan Department of Dermatology research faculty as Research Investigator in 2016. He is a member of the U-M Psoriasis Immunology and Immunogenetics Research Program.
Dr. Sarkar is pursuing research focused on the functional characterization of genetic variants in psoriasis and autoimmune skin diseases, working in collaboration with Dr. Johann Gudjonsson. Dr. Sarkar received his Ph.D. in Biochemistry from the Jadavpur University, Kolkata, India in 2010. He completed post-doctoral fellowship training in the U-M Department of Human Genetics and was recruited to the U-M Department of Dermatology's Psoriasis Immunology and Immunogenetics Research Program in 2014.