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Infection induces tissue resident memory NK cells that safeguard tissue

ABSTRACT: Tissue health is dictated by the capacity to respond to perturbations and then return to a homeostatic state. Thus, mechanisms that initiate, maintain and regulate immune responses in tissues are essential. The adaptive immune system has been ascribed a principal role in these responses, with memory and tissue-residency being cardinal features of immune protection in tissues. Whether there is a corresponding role for innate cells is unknown. Here we identify a population of innate lymphocytes that we term tissue-resident memory-like natural killer (NKRM) cells. In response to murine cytomegalovirus infection, we show that circulating NK cells are recruited to the salivary glands where they form NKRM cells, a long-lived tissue-resident population that prevents autoimmunity and safeguards organ function. Thus, NK cells develop adaptive-like features, including long-term residency in nonlymphoid tissues, to modulate inflammation, restore immune equilibrium and preserve tissue health. Modulating the functions of NKRM cells may provide new strategies to treat inflammatory and autoimmune diseases.

ORGANISM(S): Mus musculus

PROVIDER: GSE219243 | GEO | 2023/02/13

REPOSITORIES: GEO

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Memory-like Natural Killer cells become resident in non-lymphoid tissue to maintain tissue health

Project description:Tissue health is dictated by the capacity to respond to perturbations and then return to homeostasis. Mechanisms that initiate, maintain, and regulate immune responses in tissues are therefore essential. Adaptive immunity plays a key role in these responses, with memory and tissue-residency being cardinal features. A corresponding role for innate cells is unknown. Here we have identified a population of innate lymphocytes that we term tissue-resident memory-like natural killer (NKRM) cells. In response to murine cytomegalovirus infection, we show that circulating NK cells were recruited in a CX3CR1-dependent manner to the salivary glands where they formed NKRM cells, a long-lived tissue-resident population that prevented autoimmunity via TRAIL-dependent elimination of CD4+ T cells. Thus, NK cells develop adaptive-like features, including long-term residency in nonlymphoid tissues, to modulate inflammation, restore immune equilibrium and preserve tissue health. Modulating the functions of NKRM cells may provide additional strategies to treat inflammatory and autoimmune diseases.

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