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Updated: Sep 28, 2025

Teasing Out the Interplay Between Natural Killer Cells and Nociceptor Neurons
Published on: June 30, 2022
Natural Killer T Lymphocytes Integrate Innate Sensory Information and Relay Context to Effector Immune Responses
Sebastian Joyce1, Gosife Donald Okoye2, Luc Van Kaer3
1Department of Veterans Affairs, Tennessee Valley Healthcare System; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
Abstract:
It is now appreciated that a group of lymphoid lineage cells, collectively called innate-like effector lymphocytes, have evolved to integrate information relayed by the innate sensory immune system about the state of the local tissue environment and to pass on this context to downstream effector innate and adaptive immune responses. Thereby, innate functions engrained into such innate-like lymphoid lineage cells during development can control the quality and magnitude of an immune response to a tissue-altering pathogen and facilitate the formation of memory engrams within the immune system. These goals are accomplished by the innate lymphoid cells that lack antigen-specific receptors, γδ T cell receptor (TCR)-expressing T cells, and several αβ TCR-expressing T cell subsets-such as natural killer T cells, mucosal-associated invariant T cells, et cetera. Whilst we briefly consider the commonalities in the origins and functions of these diverse lymphoid subsets to provide context, the primary topic of this review is to discuss how the semi-invariant natural killer T cells got this way in evolution through lineage commitment and onward ontogeny. What emerges from this discourse is the question: Has a "limbic immune system" emerged (screaming quietly in plain sight!) out of what has been dubbed "in-betweeners"?
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