TY - JOUR
T1 - IL-22BP dictates characteristics of Peyer's patch follicleassociated epithelium for antigen uptake
AU - Jinnohara, Toshi
AU - Kanaya, Takashi
AU - Hase, Koji
AU - Sakakibara, Sayuri
AU - Kato, Tamotsu
AU - Tachibana, Naoko
AU - Sasaki, Takaharu
AU - Hashimoto, Yusuke
AU - Sato, Toshiro
AU - Watarai, Hiroshi
AU - Kunisawa, Jun
AU - Shibata, Naoko
AU - Williams, Ifor R.
AU - Kiyono, Hiroshi
AU - Ohno, Hiroshi
N1 - Funding Information:
This work was supported in part by Junior Research Associates grant from Institute of Physical and Chemical Research (to T. Jinnohara), Japan Society for the Promotion of Science KAKENHI (26460584 to T. Kanaya, 25293114 and 26116709 to K. Hase, 26293111 to J. Kunisawa, 23229004 to H. Kiyono, and 24249029 and 16H05207 to H. Ohno), Ministry of Education, Culture, Sports, Science and Technology KAKENHI (15H01165 to T. Kanaya), Japan Agency for Medical Research and Development-Core Research for Evolutional Science and Technology (15652274 to H. Ohno), Core Research for Evolutional Science and Technology from the Japan Science and Technology Agency (to H. Kiyono), The Uehara Memorial Foundation (to T. Kanaya), The Naito Foundation Natural Science Scholarship (K. Hase), and the Terumo Foundation for Life Sciences and Arts (to J. Kunisawa).
Publisher Copyright:
© 2017 Jinnohara et al.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - Interleukin-22 (IL-22) acts protectively and harmfully on intestinal tissue depending on the situation; therefore, IL-22 signaling needs to be tightly regulated. IL-22 binding protein (IL-22BP) binds IL-22 to inhibit IL-22 signaling. It is expressed in intestinal and lymphoid tissues, although its precise distribution and roles have remained unclear. In this study, we show that IL-22BP is highly expressed by CD11b+CD8α- dendritic cells in the subepithelial dome region of Peyer's patches (PPs). We found that IL-22BP blocks IL-22 signaling in the follicle-associated epithelium (FAE) covering PPs, indicating that IL-22BP plays a role in regulating the characteristics of the FAE. As expected, FAE of IL-22BP-deficient (Il22ra2-/-) mice exhibited altered properties such as the enhanced expression of mucus and antimicrobial proteins as well as prominent fucosylation, which are normally suppressed in FAE. Additionally, Il22ra2-/- mice exhibited the decreased uptake of bacterial antigens into PPs without affecting M cell function. Our present study thus demonstrates that IL-22BP promotes bacterial uptake into PPs by influencing FAE gene expression and function.
AB - Interleukin-22 (IL-22) acts protectively and harmfully on intestinal tissue depending on the situation; therefore, IL-22 signaling needs to be tightly regulated. IL-22 binding protein (IL-22BP) binds IL-22 to inhibit IL-22 signaling. It is expressed in intestinal and lymphoid tissues, although its precise distribution and roles have remained unclear. In this study, we show that IL-22BP is highly expressed by CD11b+CD8α- dendritic cells in the subepithelial dome region of Peyer's patches (PPs). We found that IL-22BP blocks IL-22 signaling in the follicle-associated epithelium (FAE) covering PPs, indicating that IL-22BP plays a role in regulating the characteristics of the FAE. As expected, FAE of IL-22BP-deficient (Il22ra2-/-) mice exhibited altered properties such as the enhanced expression of mucus and antimicrobial proteins as well as prominent fucosylation, which are normally suppressed in FAE. Additionally, Il22ra2-/- mice exhibited the decreased uptake of bacterial antigens into PPs without affecting M cell function. Our present study thus demonstrates that IL-22BP promotes bacterial uptake into PPs by influencing FAE gene expression and function.
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U2 - 10.1084/jem.20160770
DO - 10.1084/jem.20160770
M3 - Article
C2 - 28512157
AN - SCOPUS:85021854633
SN - 0022-1007
VL - 214
SP - 1607
EP - 1618
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 6
ER -