The kinase DYRK1A reciprocally regulates the differentiation of Th17 and regulatory T cells
نویسندگان
چکیده
The balance between Th17 and T regulatory (Treg) cells critically modulates immune homeostasis, with an inadequate Treg response contributing to inflammatory disease. Using an unbiased chemical biology approach, we identified a novel role for the dual specificity tyrosine-phosphorylation-regulated kinase DYRK1A in regulating this balance. Inhibition of DYRK1A enhances Treg differentiation and impairs Th17 differentiation without affecting known pathways of Treg/Th17 differentiation. Thus, DYRK1A represents a novel mechanistic node at the branch point between commitment to either Treg or Th17 lineages. Importantly, both Treg cells generated using the DYRK1A inhibitor harmine and direct administration of harmine itself potently attenuate inflammation in multiple experimental models of systemic autoimmunity and mucosal inflammation. Our results identify DYRK1A as a physiologically relevant regulator of Treg cell differentiation and suggest a broader role for other DYRK family members in immune homeostasis. These results are discussed in the context of human diseases associated with dysregulated DYRK activity.
منابع مشابه
All-trans Retinoic Acid Regulates the Balance of Treg-Th17 Cells through ERK and P38 Signaling Pathway
متن کامل
MiR-9-5p and miR-106a-5p dysregulated in CD4+ T-cells of multiple sclerosis patients and targeted essential factors of T helper17/regulatory T-cells differentiation
Objective(s): Multiple sclerosis (MS) is considered as a chronic type of an inflammatory disease characterized by loss of myelin of CNS.Recent evidence indicates that Interleukin 17 (IL-17)-producing T helper cells (Th17 cells) population are increased and regulatory T cells (Treg cells) are decreased in MS. Despite extensive research in understanding the mechanism of Th17 and Treg differentiat...
متن کاملP 51: The Role of T Helper 17 in Pathogenesis of Multiple Sclerosis
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) which causes demyelination of the nerve fibers. The etiology of this disease is not well understood but it is believed that T helpers play a central role in MS. Numerous findings support the view that Th17 cells play an essential role in pathogenesis of MS and IL-17 secreting T (Th17) cells have a role in infla...
متن کاملInactivated Mycobacterium phlei inhalation ameliorates allergic asthma through modulating the balance of CD4+CD25+ regulatory T and Th17 cells in mice
Objective(s): Th2 response is related to the aetiology of asthma, but the underlying mechanism is unclear. To address this point, the effect of nebulized inhalation of inactivated Mycobacterium phlei on modulation of asthmatic airway inflammation was investigated. Materials and Methods: 24 male BALB/c mice were randomly divided into three groups: control group (Group A), asthma model group (G...
متن کاملFyn promotes Th17 differentiation by regulating the kinetics of RORγt and Foxp3 expression.
Th17 cells constitute a proinflammatory CD4(+) T cell subset that is important for microbial clearance, but also are implicated as propagators of various autoimmune pathologies. Evidence suggests that Th17 cells share common progenitors with immunosuppressive CD4(+) inducible regulatory T cells (T(REG)) and that the developmental pathways of these two subsets are reciprocally regulated. In this...
متن کامل