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Tissue-resident NK cells do their own glandscaping
Jacob A Myers1, Shanelle P Reilly1, Laurent Brossay1
1Division of Biology and Medicine, Department of Molecular Microbiology and Immunology, Brown University, Providence, RI, USA.
The Journal of Experimental Medicine
|January 3, 2025
Summary
Salivary gland tissue-resident natural killer (trNK) cells develop from conventional NK (cNK) cells, not ILC1 cells. TGF-β and IL-15 signaling promote their tissue residency and cytotoxic function.
Area of Science:
- Immunology
- Cell Biology
- Tissue-Specific Immunity
Background:
- Natural killer (NK) cells play crucial roles in immune surveillance and tissue homeostasis.
- The precise origin and developmental pathways of tissue-resident NK cells remain incompletely understood.
- Salivary glands represent a unique immunological microenvironment with resident immune cell populations.
Purpose of the Study:
- To elucidate the developmental origin of salivary gland tissue-resident NK cells (trNK).
- To differentiate trNK cells from other innate lymphoid cells, specifically type 1 innate lymphoid cells (ILC1).
- To identify the key molecular mechanisms driving trNK cell tissue residency and function.
Main Methods:
- Flow cytometry and single-cell RNA sequencing to characterize immune cell populations.
- In vivo studies using mouse models to track cell development and residency.
- In vitro assays to investigate cytokine signaling pathways (TGF-β, IL-15) and their effects on cell function.
Main Results:
- Salivary gland trNK cells demonstrably originate from conventional NK (cNK) cells.
- trNK cells are developmentally distinct from ILC1 cells, supporting a unique lineage.
- Continuous autocrine transforming growth factor-beta (TGF-β) signaling is essential for salivary gland tissue residency.
- Interleukin-15 (IL-15) synergizes with TGF-β to enhance Hobit-dependent cytotoxicity in trNK cells.
Conclusions:
- Salivary gland trNK cells arise from cNK cells, establishing a distinct lineage separate from ILC1s.
- Autocrine TGF-β signaling is a critical driver of trNK cell tissue residency in salivary glands.
- Combined TGF-β and IL-15 signaling pathways regulate the cytotoxic potential of salivary gland trNK cells.
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