TY - JOUR
T1 - Dietary antigens suppress the proliferation of type 2 innate lymphoid cells by restraining homeostatic IL-25 production
AU - Lee, Minji
AU - Ko, Hyun Ja
AU - Hong, Sung Wook
AU - Park, Jungeun
AU - Ham, Seokjin
AU - Kim, Mingyu
AU - Kwon, Dong il
AU - Lee, Myeong seok
AU - Roh, Tae Young
AU - Soon Kim, Kwang
AU - Lee, You Jeong
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85129684150&partnerID=8YFLogxK
U2 - 10.1038/s41598-022-11466-4
DO - 10.1038/s41598-022-11466-4
M3 - Article
C2 - 35523930
AN - SCOPUS:85129684150
SN - 2045-2322
VL - 12
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 7443
ER -