%0 Journal Article
%T Tonic type 2 immunity is a critical tissue checkpoint controlling autoimmunity in the skin.
%A Lee JE
%A Kim M
%A Ochiai S
%A Kim SH
%A Yeo H
%A Bok J
%A Kim J
%A Park M
%A Kim D
%A Lamiable O
%A Lee M
%A Kim MJ
%A Kim HY
%A Ronchese F
%A Kwon SW
%A Lee H
%A Kim TG
%A Chung Y
%J Cell Rep
%V 43
%N 7
%D 2024 Jul 23
%M 38900635
暂无%R 10.1016/j.celrep.2024.114364
%X Immunoregulatory mechanisms established in the lymphoid organs are vital for preventing autoimmunity. However, the presence of similar mechanisms in non-lymphoid tissues remains unclear. Through transcriptomic and lipidomic analyses, we find a negative association between psoriasis and fatty acid metabolism, as well as Th2 signature. Homeostatic expression of liver X receptor (LXR) and peroxisome proliferator-activated receptor gamma (PPARγ) is essential for maintaining fatty acid metabolism and for conferring resistance to psoriasis in mice. Perturbation of signal transducer and activator of transcription 6 (STAT6) diminishes the homeostatic levels of LXR and PPARγ. Furthermore, mice lacking STAT6, interleukin 4 receptor alpha (IL-4Rα), or IL-13, but not IL-4, exhibit increased susceptibility to psoriasis. Under steady state, innate lymphoid cells (ILCs) are the primary producers of IL-13. In human skin, inhibiting tonic type 2 immunity exacerbates psoriasis-like inflammation and IL-17A, while activating LXR or PPARγ inhibits them. Hence, we propose that tonic type 2 immunity, driven by IL-13-producing ILCs, represents a crucial tissue checkpoint that represses autoimmunity and maintains lipid homeostasis in the skin.