| Autor: |
Saager ES; Center for Translational Immunology, University Medical Centre Utrecht, Utrecht, Netherlands., van Stigt AH; Center for Translational Immunology, University Medical Centre Utrecht, Utrecht, Netherlands., Lerkvaleekul B; Division of Rheumatology, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Lutter L; Center for Translational Immunology, University Medical Centre Utrecht, Utrecht, Netherlands.; Department of Pathology, Amsterdam University Medical Centre, Amsterdam, Netherlands., Hellinga AH; Center for Translational Immunology, University Medical Centre Utrecht, Utrecht, Netherlands., van der Wal MM; Center for Translational Immunology, University Medical Centre Utrecht, Utrecht, Netherlands., Bont LJ; Center for Translational Immunology, University Medical Centre Utrecht, Utrecht, Netherlands.; Department of Paediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital/University Medical Center Utrecht, Utrecht, Netherlands.; ReSViNET foundation, Zeist, Netherlands., Leusen JH; Center for Translational Immunology, University Medical Centre Utrecht, Utrecht, Netherlands., Van't Land B; Center for Translational Immunology, University Medical Centre Utrecht, Utrecht, Netherlands.; CoE Immunology, Danone Global Research & Innovation Center, Utrecht, Netherlands., van Wijk F; Center for Translational Immunology, University Medical Centre Utrecht, Utrecht, Netherlands. |
| Abstrakt: |
Breastfeeding provides important immunological benefits to the neonate, but how the different immunoactive components in breastmilk contribute to immunity remains poorly understood. Here, we characterized human breastmilk T cells using single-cell RNA-Seq and flow cytometry. Breastmilk contained predominantly memory T cells, with expression of immune signaling genes, high proliferation, and an effector Th1/cytotoxic profile with high cytokine production capacities. Elevated activation was balanced by an enriched Treg population and immune regulatory markers in conventional memory T cells. Gene and surface expression of tissue-residency markers indicate that breastmilk T cells represented tissue-adapted rather than circulatory T cells. In addition, breastmilk T cells had a broad homing profile and higher activation markers in these migratory subsets. The partly overlapping transcriptome profile between breastmilk and breast tissue T cells, particularly cytotoxic T cells, might support a role in local immune defense in the mammary gland. However, unique features of breastmilk, such as Tregs, might imply an additional role in neonatal immune support. We found some correlations between the breastmilk T cell profile and clinical parameters, most notably with maternal and household factors. Together, our data suggest that breastmilk contains an adapted T cell population that exerts their function in specific tissue sites. |
