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Epithelial-myeloid exchange of MHC class II constrains immunity and microbiota composition.
- Source :
-
Cell reports [Cell Rep] 2021 Nov 02; Vol. 37 (5), pp. 109916. - Publication Year :
- 2021
-
Abstract
- Intestinal epithelial cells (IECs) have long been understood to express high levels of major histocompatibility complex class II (MHC class II) molecules but are not considered canonical antigen-presenting cells, and the impact of IEC-MHC class II signaling on gut homeostasis remains enigmatic. As IECs serve as the primary barrier between underlying host immune cells, we reasoned that IEC-intrinsic antigen presentation may play a role in responses toward the microbiota. Mice with an IEC-intrinsic deletion of MHC class II (IEC <superscript>ΔMHC class II</superscript> ) are healthy but have fewer microbial-bound IgA, regulatory T cells (Tregs), and immune repertoire selection. This was associated with increased interindividual microbiota variation and altered proportions of two taxa in the ileum where MHC class II on IECs is highest. Intestinal mononuclear phagocytes (MNPs) have similar MHC class II transcription but less surface MHC class II and are capable of acquiring MHC class II from IECs. Thus, epithelial-myeloid interactions mediate development of adaptive responses to microbial antigens within the gastrointestinal tract.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Antigens, Bacterial immunology
Antigens, Bacterial metabolism
Bacteria growth & development
Bacteria metabolism
Cell Line
Colitis immunology
Colitis metabolism
Colitis microbiology
Disease Models, Animal
Epithelial Cells metabolism
Epithelial Cells microbiology
Female
Histocompatibility Antigens Class II metabolism
Host-Pathogen Interactions
Ileum immunology
Ileum metabolism
Immunoglobulin A immunology
Immunoglobulin A metabolism
Male
Mice, Inbred C57BL
Mice, Knockout
Mononuclear Phagocyte System metabolism
Mononuclear Phagocyte System microbiology
Myeloid Cells metabolism
Myeloid Cells microbiology
Signal Transduction
T-Lymphocytes, Regulatory immunology
T-Lymphocytes, Regulatory metabolism
Mice
Adaptive Immunity
Bacteria immunology
Epithelial Cells immunology
Gastrointestinal Microbiome
Histocompatibility Antigens Class II immunology
Ileum microbiology
Immunity, Mucosal
Mononuclear Phagocyte System immunology
Myeloid Cells immunology
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 37
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 34731608
- Full Text :
- https://doi.org/10.1016/j.celrep.2021.109916