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

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

Abstract

Goal 1: We seek to investigate the prevalence and significance of allergy-associated cytokines in human autoinflammatory diseases. In Fiscal Year (FY) 2022 we published a review of this topic, based on our investigations on the prevalence of and mechanisms underlying allergy-associated phenotypes in patients with known pathogenic mutations causing monogenic disorders of autoimmunity and autoinflammation. Goal 2: We seek to understand the mechanisms through which allergy-associated cytokines and in particular IL-9 promote pathology in autoimmune diseases. In FY2022, we continued our collaboration with NHLBI, to study the role of Th9 cells in the human autoimmune disease psoriasis and have uncovered associations with cardiovascular disease that we are exploring mechanistically. We utilized this collaboration to publish a manuscript on the role of noninvasive imaging technique in dissecting mechanisms of cardiovascular inflammatory disease in psoriasis. Goal 3: We seek to understand the basic mechanisms through which atopic cytokines, including IL-9, are regulated. In collaboration with the 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 FY2022, we performed follow up studies for a second manuscript investigating mechanisms of IL-9 regulation in human cells; this manuscript is under revision for publication in a major scientific journal.