Institute of Development, Aging and Cancer, Tohoku University

Research

Seminars and Symposia

IDAC Seminar, 22 June 2015

Secretariat, Alumni Association, IDAC
Date Monday,22 June 2015, 17:00~
Room Seminar-shitsu 1, IDAC Research building 7F
Title Biological homeostatic mechanism by nuclear IκB family molecules
Speaker Dr. Takashi Maruyama
Affiliation Gifu University
Person-in-charge Koetsu Ogasawara Dept. of Immunobiology (ext.8579)
Abstract IκB-ζ, a member of nuclear IκB family protein, has first identified in macrophages in response to LPS stimulation. IκB-ζ have ankyrin repeat domain, which plays an important role for making complex with NF-κB and control their transcriptional effect in nuclear.
It has been reported that IκB-ζ deficient mice have resistant to experimental autoimmune encephalomyelitis (EAE), because less Th17 cells differentiations. However, Dr. Muta has reported that IκB-ζ deficient mice caused Sjögren's like autoimmune disease with age, because enhanced apoptosis in keratinocytes in lacrimal grand (Immunity 38;450-60:2013). Thus, IκB-ζ is important for both maintain immune homeostasis and develop inflammations. Interestingly, in this Sjögren's like autoimmune disease has shown that T cells play an important role for develop inflammation. However, it is still unclear whether deficiency of IκB-ζ in T cells reduced immune regulatory functions.
Therefore, we generate T cell specific IκB-ζ deficient (cKO) mice and found that more IFN-γ production and reduce Tregs’ immune regulatory activity. When cKO mice become older (-6 month old), they have splenomegaly and observe lympho infiltration in various tissue. However, cKO-mice dose not develop Sjögren's like autoimmune disease with age. Thus, IκB-ζ in T cells were also important for maintaining immune homeostasis, but it’s not a direct factor for develop Sjögren's like autoimmune disease.
Previously, We focus on IκBNS, the most similar homolog of IκB-ζ. IκBNS deficient mice do not exhibit an inflammatory dysregulation with ages (including Sjögren's like autoimmune disease). Interestingly, IκBNS deficient mice show resistant against development of Th17 dependent EAE, because reduce Th17 cells differentiation in IκBNS deficient T cells. Thus, we believe that IκBNS has a potential of new therapeutic target of Th17 dependent autoimmune diseases.