Circulatory proteins shape microglia state and boost phagocytosis

Nannan Lu(Neurosciences Institute), Patricia Moran‐Losada(Neurosciences Institute), Oliver Hãhn(Neurosciences Institute), Aryaman Saksena(Neurosciences Institute), Emma Tapp(Neurosciences Institute), Jean Paul Chadarevian(University of California, Irvine), Wentao Dong(Stanford University), Sophia M. Shi(Neurosciences Institute), Steven R. Shuken(Harvard University), Ian H. Guldner(Neurosciences Institute), Wenshu Zeng(Hong Kong University of Science and Technology), Ning-Sum To, Pui Shuen Wong(Hong Kong University of Science and Technology), Jonathan Hasselmann(University of California, Irvine), Hayk Davtyan(University of California, Irvine), Jerry Sun(Neurosciences Institute), Lulin Li(Stanford University), Jian Luo(Stanford University), Andrew C. Yang(Gladstone Institutes), Qing Yun Li(Washington University in St. Louis), Tom H. Cheung(Hong Kong University of Science and Technology), Monther Abu-Remaileh(Stanford University), Mathew Blurton‐Jones(University of California, Irvine), Tony Wyss‐Coray(Neurosciences Institute)
bioRxiv (Cold Spring Harbor Laboratory)
October 2, 2024
10.1101/2024.09.30.615861
Cited by 10Open Access
Full Text

Abstract

Summary Microglia, the brain’s immune cells, are highly responsive to their local environment. Given that circulatory proteins can enter the brain, we asked whether microglia are responsive to such proteins. Here, we identify a stable population of microglia specialized to take up circulatory proteins in a region-specific manner under physiological conditions; human hematopoietic stem cell-derived microglia replacing endogenous microglia in chimeric mice show similar regional specialization. Plasma-positive microglia are characterized by prominent expression of genes related to innate immunity and antigen presentation and exhibit high metabolic and phagocytic activity. This activity is dependent, in part, on microglial uptake and accumulation of circulatory Apolipoprotein AI (ApoA-I). Our findings thus identify a new model of communication between brain and periphery through specialized microglia.

Related Papers

No related papers found

Powered by citation graph analysis