The Regulation and Roles of Atopic Cytokines in Autoimmune and Autoinflammatory Diseases

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications, trials & patents

Abstract

The main focus of this project is to study the regulation and roles of atopic cytokines in the context of autoimmune and autoinflammatory diseases. We seek to do this by studying patients with syndromic atopy and autoimmunity/autoinflammation, utilizing mouse models of atopic and autoimmune disease, and investigating the basic mechanisms by which these cytokines are regulated and act on their target cells. Goal 1: We seek to investigate the prevalence and significance of allergy-associated cytokines in human autoinflammatory diseases. We are also establishing a cohort of patients with autoinflammatory disease (AD) and syndromic allergic features (AF), with no known pathologic mutations. In Fiscal Year (FY) 2021 we completed our investigation of the prevalence of allergy-associated phenotypes in patients with known pathogenic mutations causing monogenic disorders of autoinflammation. A manuscript based on these findings was published in FY2021 Goal 2: We seek to understand the mechanisms through which allergy-associated cytokines and in particular IL-9 promote pathology in autoimmune diseases. In FY 2021, we collaborated with National Heart Lung and Blood Institute (NHLBI), to study the role of Th9 cells in the human autoimmune disease psoriasis and continued to explore the mechanisms underlying extracutaneous disease. Goal 3: We seek to understand the basic mechanisms through which atopic cytokines, including IL-9, are regulated. In collaboration with the National Institute for Arthritis and Musculoskeletal and Skin Diseases (NIAMS), we have defined a set of genes that are highly expressed in IL-9-producing T cells, or Th9 cells. We also identified critical regions of noncoding regulatory DNA, that are critical for inducing expression of the Il9 gene. These results were published in Immunity in 2019. In FY 2021, we performed follow up studies for a second manuscript investigating mechanisms of IL-9 regulation in human cells; this manuscript is in preparation.