Epithelial-myeloid exchange of MHC class II constrains immunity and microbiota composition
W. Zac Stephens,
Jason L. Kubinak,
Arevik Ghazaryan,
Kaylyn M. Bauer,
Rickesha Bell,
Kate Buhrke,
Tyson R. Chiaro,
Allison M. Weis,
William W. Tang,
Josh K. Monts,
Ray Soto,
H. Atakan Ekiz,
Ryan M. O’Connell,
June L. Round
Affiliations
W. Zac Stephens
University of Utah School of Medicine, Department of Pathology, Division of Microbiology and Immunology, Salt Lake City, UT 84112, USA
Jason L. Kubinak
University of South Carolina School of Medicine, Department of Pathology, Microbiology and Immunology, Columbia, SC 29209, USA
Arevik Ghazaryan
University of Utah School of Medicine, Department of Pathology, Division of Microbiology and Immunology, Salt Lake City, UT 84112, USA
Kaylyn M. Bauer
University of Utah School of Medicine, Department of Pathology, Division of Microbiology and Immunology, Salt Lake City, UT 84112, USA
Rickesha Bell
University of Utah School of Medicine, Department of Pathology, Division of Microbiology and Immunology, Salt Lake City, UT 84112, USA
Kate Buhrke
University of Utah School of Medicine, Department of Pathology, Division of Microbiology and Immunology, Salt Lake City, UT 84112, USA
Tyson R. Chiaro
University of Utah School of Medicine, Department of Pathology, Division of Microbiology and Immunology, Salt Lake City, UT 84112, USA
Allison M. Weis
University of Utah School of Medicine, Department of Pathology, Division of Microbiology and Immunology, Salt Lake City, UT 84112, USA
William W. Tang
University of Utah School of Medicine, Department of Pathology, Division of Microbiology and Immunology, Salt Lake City, UT 84112, USA
Josh K. Monts
University of Utah School of Medicine, Department of Pathology, Division of Microbiology and Immunology, Salt Lake City, UT 84112, USA; University of South Carolina School of Medicine, Department of Pathology, Microbiology and Immunology, Columbia, SC 29209, USA; Izmir Institute of Technology, Molecular Biology and Genetics Department, Gulbahce, Izmir 35430, Turkey; University of Utah School of Medicine, Flow Cytometry Core, Health Sciences Center, Salt Lake City, UT 84112, USA
Ray Soto
University of Utah School of Medicine, Department of Pathology, Division of Microbiology and Immunology, Salt Lake City, UT 84112, USA
H. Atakan Ekiz
University of Utah School of Medicine, Department of Pathology, Division of Microbiology and Immunology, Salt Lake City, UT 84112, USA; Izmir Institute of Technology, Molecular Biology and Genetics Department, Gulbahce, Izmir 35430, Turkey
Ryan M. O’Connell
University of Utah School of Medicine, Department of Pathology, Division of Microbiology and Immunology, Salt Lake City, UT 84112, USA; Corresponding author
June L. Round
University of Utah School of Medicine, Department of Pathology, Division of Microbiology and Immunology, Salt Lake City, UT 84112, USA; Corresponding author
Summary: 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 (IECΔMHC class II) 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.
