TY  - JOUR
A1  - Bachmann, Malte
A1  - Scheiermann, Patrick
A1  - Härdle, Lorena
A1  - Pfeilschifter, Josef
A1  - Mühl, Heiko
T1  - IL-36γ/IL-1F9, an innate T-bet target in myeloid cells
T2  - Journal of biological chemistry
N2  - Background: The transcription factor T-bet is pivotal for initiation of Th1-related immunoactivation. Identification of novel genes directly regulated by T-bet is crucial.
Results: Genome-wide analysis and subsequent experiments revealed that T-bet up-regulates IL-36γ/IL-1F9 in myeloid cells.
Conclusion: IL-1-related IL-36γ is a direct T-bet target in myeloid cells.
Significance: Observations suggest that IL-36γ , besides IFNγ, contributes to T-bet functions in immunopathology
By concerted action in dendritic (DC) and T cells, T-box expressed in T cells (T-bet, Tbx21) is pivotal for initiation and perpetuation of Th1 immunity. Identification of novel T-bet-regulated genes is crucial for further understanding the biology of this transcription factor. By combining siRNA technology with genome-wide mRNA expression analysis, we sought to identify new T-bet-regulated genes in predendritic KG1 cells activated by IL-18. One gene robustly dependent on T-bet was IL-36γ, a recently described novel IL-1 family member. Promoter analysis revealed a T-bet binding site that, along with a κB site, enables efficient IL-36γ induction. Using knock-out animals, IL-36γ reliance on T-bet was extended to murine DC. IL-36γ expression by human myeloid cells was confirmed using monocyte-derived DC and M1 macrophages. The latter model was employed to substantiate dependence of IL-36γ on endogenous T-bet in human primary cells. Ectopic expression of T-bet likewise mediated IL-36γ production in HaCaT keratinocytes that otherwise lack this transcription factor. Additional experiments furthermore revealed that mature IL-36γ has the capability to establish an inflammatory gene expression profile in human primary keratinocytes that displays enhanced mRNA levels for TNFα, CCL20, S100A7, inducible NOS, and IL-36γ itself. Data presented herein shed further light on involvement of T-bet in innate immunity and suggest that IL-36γ, besides IFNγ, may contribute to functions of this transcription factor in immunopathology.
KW  - Dendritic Cells
KW  - Gene Regulation
KW  - Innate Immunity
KW  - Interleukin
KW  - Macrophages
KW  - Interleukin-1
KW  - Interleukin-36
KW  - T-bet
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/76647
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-766473
SN  - 0021-9258
VL  - 287
IS  - 50
SP  - 41684
EP  - 41696
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -