IL-22BP dictates characteristics of Peyer's patch follicle-associated epithelium for antigen uptake

• Authors: Toshi Jinnohara, Institute of Physical and Chemical Research; Takashi Kanaya, Institute of Physical and Chemical Research; Koji Hase, Keio University; Sayuri Sakakibara, Institute of Physical and Chemical Research; Tamotsu Kato, Institute of Physical and Chemical Research; Naoko Tachibana, Institute of Physical and Chemical Research; Takaharu Sasaki, Institute of Physical and Chemical Research; Yusuke Hashimoto, Institute of Physical and Chemical Research; Toshiro Sato, Keio University; Hiroshi Watarai, University of Tokyo; Jun Kunisawa, University of Tokyo; Naoko Shibata, University of Tokyo; Hiroshi Kiyono, University of Tokyo; Ifor Williams, Emory University; Hiroshi Ohno, Institute of Physical and Chemical Research
• Report Title: Journal of Experimental Medicine
• Publisher: Rockefeller University Press
• Publication Date: 2017-06-01
• Type of Work: Report
• Publisher DOI: http://doi.org/10.1084/jem.20160770
• Subjects: Health Sciences, Pathology; Health Sciences, General
• Keywords: Science & Technology; Life Sciences & Biomedicine; Immunology; Medicine, Research & Experimental; Research & Experimental Medicine; INNATE LYMPHOID-CELLS; INTESTINAL M CELLS; FACTOR SPI-B; BINDING-PROTEIN; STEM-CELLS; IN-VITRO; SALMONELLA-TYPHIMURIUM; BACTERIAL PATHOGENS; HOST-DEFENSE; GROWTH-RATE

Abstract

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.