Immunity system complexity: sentinel cell activation (Introduction)

by David Turell , Friday, March 31, 2023, 23:37 (602 days ago) @ David Turell

Complex molecular interactions:

https://www.sciencemagazinedigital.org/sciencemagazine/library/item/31_march_2023/40914...

"Efficient host defense relies on the ability to mount context-dependent immune responses. Dendritic cells (DCs) sense pathogens and tissue damage and subsequently migrate to lymph nodes to present antigens to naive T cells. Through the production of cytokines, DCs further instruct other immune cells about which type of immune response is needed. For example, DC-derived interleukin-23 (IL-23) in the skin promotes efficient defense against Candida albicans and Staphylococcus aureus infections, but it also drives psoriasislike skin inflammation. Nociceptors are somatosensory neurons that innervate barrier organs and detect noxious stimuli, including mechanical injury, reactive chemicals, inflammatory mediators, and pathogens. Nociceptors relay noxious stimuli to the brain as pain or itching sensation and release neuropeptides, which can influence immune cells. On page 1315 of this issue, Hanč et al. report the identification of multiple mechanisms by which nociceptors can regulate DCs in the skin.

"The same research group had previously shown that nociceptors potentiate the production of the inflammatory cytokine IL-23 from type 1 and type 2 conventional DCs (cDC1 and cDC2) in imiquimod-induced skin inflammation in mice (3). cDC1s are potent activators of CD8+ T cells and promote T helper 1 (TH1) differentiation, for instance through the production of IL-12. cDC2s efficiently promote TH2 and TH17 cell differentiation, the latter in part through the production of IL-23.

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"The observation that nociceptor-derived CGRP can elicit an enhanced sentinel state in DCs before they encounter pathogens is intriguing and necessitates the determination of whether nociceptor-derived signals affect the development and homeostasis of DCs in the steady state or solely in the context of inflammation or pathogenic insult. In inflammation, nociceptor-derived CCL2 could aid the replenishment of DCs by recruiting DC progenitors from the circulation. Sensory neurons innervate various tissues, including lymphoid organs, suggesting that neuronal modulation of DCs could be site specific. DC-derived inflammatory cytokines can activate nociceptors to promote itching. Therefore, DC-nociceptor cross-talk could amplify unwanted sensory or inflammatory responses in settings of chronic pain. Thus, the study of Hanč et al. opens new avenues for studying neuroimmune interactions in inflammation."

Comment: what I skipped is a highly technical exposition of complex molecular reactions to stimuli that require a highly alerted immune system at several levels. I showed thess paragraphs to give some sense of the complexity. Not by chance.