Dietary antigens suppress the proliferation of type 2 innate lymphoid cells by restraining homeostatic IL-25 production

Minji Lee, Hyun Ja Ko, Sung Wook Hong, Jungeun Park, Seokjin Ham, Mingyu Kim, Dong il Kwon, Myeong seok Lee, Tae Young Roh, Kwang Soon Kim, You Jeong Lee

Research output: Contribution to journalArticlepeer-review


Dietary antigens affect the adaptive immunity of the host by inducing regulatory T cells and IgE-producing B cells. However, their roles in innate immune compartments such as innate lymphoid cells (ILCs) and intestinal epithelial cells (IECs) are unclear. Here, using antigen-free (AF) mice, which are germ-free (GF) mice fed with amino-acid-based diet, we found dietary proteins suppress the development of GATA-3-expressing ILC2s independent of the adaptive immune cells. These cells produce more type 2 cytokines and upregulated proliferation and activation markers such as Ki-67, CD69, and CD25. With this, AF mice had increased expressions of tuft cell-specific transcripts such as Il25, Il33, Dclk1, Trpm5, and Pou2f3 in IECs. Accordingly, expanded ILC2s upregulated IL-17RB, a receptor of IL-25, and their proliferation was blocked by IL-25 neutralizing or IL-17RB blocking antibodies. These results suggest a new dialogue between dietary antigens, IECs, and ILCs in which dietary antigens suppress ILC2 activation and proliferation by restraining homeostatic IL-25 production, potentially limiting type 2 immunity by food antigens.

Original languageEnglish
Article number7443
JournalScientific Reports
Issue number1
StatePublished - Dec 2022

Bibliographical note

Funding Information:
Charles D. Surh, who made a significant contribution to the research, passed away during the project development. This research has been supported by the Korean Ministry of Science, Information/Communication Technology, and Future Planning (2021R1A4A1031754, 2021R1F1A1054395 and 2022R1A2C1007692).

Publisher Copyright:
© 2022, The Author(s).


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