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Astrocytic interleukin-3 programs microglia and limits Alzheimer's disease
Cameron S McAlpine 1 2 3, Joseph Park 4, Ana Griciuc 4, Eunhee Kim 4, Se Hoon Choi 4, Yoshiko Iwamoto 1, Máté G Kiss 1, Kathleen A Christie 5, Claudio Vinegoni 1, Wolfram C Poller 1 2, John E Mindur 1, Christopher T Chan 1, Shun He 1, Henrike Janssen 1, Lai Ping Wong 6 7, Jeffrey Downey 1, Sumnima Singh 1, Atsushi Anzai 1, Florian Kahles 1, Mehdi Jorfi 4, Paolo Fumene Feruglio 8, Ruslan I Sadreyev 6 9, Ralph Weissleder 1, Benjamin P Kleinstiver 5, Matthias Nahrendorf 1, Rudolph E Tanzi 10, Filip K Swirski 11 12
Abstract:
...Here we show, in humans and mice, that astrocyte-sourced interleukin-3 (IL-3) programs microglia to ameliorate the pathology of AD. Upon recognition of Aβ deposits, microglia increase their expression of IL-3Rα-the specific receptor for IL-3 (also known as CD123)-making them responsive to IL-3. Astrocytes constitutively produce IL-3, which elicits transcriptional, morphological, and functional programming of microglia to endow them with an acute immune response program, enhanced motility, and the capacity to cluster and clear aggregates of Aβ and tau. These changes restrict AD pathology and cognitive decline. Our findings identify IL-3 as a key mediator of astrocyte-microglia cross-talk and a node for therapeutic intervention in AD.
