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Updated: Jan 11, 2026
Co-Culture of Murine Small Intestine Epithelial Organoids with Innate Lymphoid Cells
Published on: March 23, 2022
Milk-derived osteopontin influences the composition of the intestinal intraepithelial lymphocyte compartment
Kathleen G McClanahan1, Jayden Capella1, Jennifer A Gaddy2
1Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, United States.
Insights
Milk osteopontin is crucial for the development of intestinal intraepithelial lymphocytes (IELs) in mice. However, disruptions in IELs did not increase susceptibility to intestinal inflammation.
Area of Science:
- Immunology
- Developmental Biology
- Gastroenterology
Background:
- Osteopontin (OPN) is a pleiotropic protein found in various tissues and bodily fluids, including breast milk.
- While endogenous OPN affects intestinal intraepithelial lymphocytes (IELs), the role of milk-derived OPN in immune cell development is largely unknown.
- Breast milk OPN is recognized for its influence on infant intestinal and brain development.
Purpose of the Study:
- To investigate the specific role of milk-derived osteopontin in the development of intestinal intraepithelial lymphocytes (IELs).
- To determine if altered IEL compartments due to lack of milk OPN impact susceptibility to intestinal inflammation.
Main Methods:
- Utilized mouse models genetically engineered to lack osteopontin expression.
- Analyzed the development and composition of IEL populations in juvenile and adult mice.
- Assessed susceptibility to chemically induced (DSS) and infection-induced (Citrobacter rodentium) intestinal inflammation.
Main Results:
- Milk-derived osteopontin significantly impacts the development of IELs in both juvenile and adult mice.
- The most pronounced effects were observed in IELs expressing the CD8αα co-receptor.
- Despite alterations in IEL compartments, mice lacking OPN did not exhibit increased susceptibility to DSS-induced colitis or Citrobacter rodentium infection.
Conclusions:
- Milk osteopontin plays a vital role in the proper development of intestinal intraepithelial lymphocytes.
- The functional significance of OPN-mediated alterations in IELs regarding intestinal immune homeostasis requires further investigation.
- The absence of milk OPN does not compromise the host's defense against common models of intestinal inflammation.
Abstract:
Osteopontin is a protein with many physiological roles widely expressed by many cell types, tissues, and bodily fluids, including breastmilk. The functions of breastmilk osteopontin are not clearly defined, however, it is known to impact intestinal and brain development in infants. Although it has been shown that endogenous osteopontin influences the survival of intestinal intraepithelial lymphocytes (IEL), the impact of milk osteopontin on developing intestinal immune cells remains unclear. In this report, mouse models lacking expression of osteopontin were used to demonstrate that milk-derived osteopontin is important for the development of IELs, with observed effects in both juvenile and adult mice. These changes are most prevalent in IELs expressing CD8αα: however, the impact of these alterations is unclear, as mice with disrupted IEL compartments are not more susceptible to intestinal inflammation induced by DSS or Citrobacter rodentium infection.
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