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Human breastmilk memory T cells throughout lactation manifest activated tissue-oriented profile with prominent regulation
Elise S. Saager, Arthur H. van Stigt, Butstabong Lerkvaleekul, Lisanne Lutter, Anneke H. Hellinga, M. Marlot van der Wal, Louis J. Bont, Jeanette H.W. Leusen, Belinda van’t Land, Femke van Wijk, the Protection against Respiratory tract infections through human Milk Analysis (PRIMA) group
Elise S. Saager, Arthur H. van Stigt, Butstabong Lerkvaleekul, Lisanne Lutter, Anneke H. Hellinga, M. Marlot van der Wal, Louis J. Bont, Jeanette H.W. Leusen, Belinda van’t Land, Femke van Wijk, the Protection against Respiratory tract infections through human Milk Analysis (PRIMA) group
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Research Article Immunology

Human breastmilk memory T cells throughout lactation manifest activated tissue-oriented profile with prominent regulation

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Abstract

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.

Authors

Elise S. Saager, Arthur H. van Stigt, Butstabong Lerkvaleekul, Lisanne Lutter, Anneke H. Hellinga, M. Marlot van der Wal, Louis J. Bont, Jeanette H.W. Leusen, Belinda van’t Land, Femke van Wijk, the Protection against Respiratory tract infections through human Milk Analysis (PRIMA) group

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Figure 7

Partial overlap of breastmilk with breast tissue T cells.

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Partial overlap of breastmilk with breast tissue T cells.
Clustering of ...
Clustering of breastmilk T cells with the immune cell subsets from healthy breast tissue extracted from 2 publicly available single-cell RNA-Seq datasets, with breastmilk T cells in orange (n = 7), breast tissue cells from Pal et al. (39) in blue (n = 12) and breast tissue CD45+ immune cells from Azizi et al. (40) in green (n = 10). (A) UMAP showing cluster annotation. (B) UMAP showing the original cluster annotation of the breastmilk T cells (colors) projected onto the combined clustering space of breastmilk and breast tissue (black). (C) UMAP gene expression (log-normalized) projections for CD3D, CD4, and CD8A. (D) Frequency of each of the 3 datasets for the main cell types identified in A and C. (E) Violin plots comparing gene expression (log-normalized) of CD4, CD8A, FOXP3, CTLA-4, ITGB1 (integrin β1), and CCL5 between the breastmilk and breast tissue datasets for each of the major T cell subsets.

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ISSN 2379-3708

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