Biology subjects

Badrani, J. H.

Publications and source records attributed to Badrani, J. H..

3 recordsLinked to original sources

bioRxiv2024

FcγR- and CD9-dependent synapse engulfing microglia in the thalamus drives cognitive impairment following cortical brain injury

Various states of microglia appear in neuroinflammation, but their impact on brain function and behavior is not fully understood. Here we report that synapse engulfing microglia in the thalamus are crucial for cognitive impairment after cortical brain injury. Region-specific manipulations of reactive microglia in the chronic phase of injuries showed that microglial changes in the thalamus, but not in the hippocampus, impaired recognition memory. Single-cell RNA-sequencing analysis revealed the enrichment of synapse engulfing microglia in the thalamus, which developed in a CD9-dependent manner and caused synaptic loss and recognition memory deficits. In the thalamus, the blood-brain barrier was disrupted, and extravasated {gamma}-immunoglobulins (IgG) co-localized with synapse engulfing microglia. Fc{gamma} receptor III blockade in the thalamus reduced synapse engulfing microglia, synapse loss, and recognition memory deficits. These findings demonstrate that the induction of synapse engulfing microglia in the thalamus by extravasated IgG/Fc{gamma}RIII and CD9 signals causes recognition memory deficits after cortical brain injury.

immunology↗

bioRxiv2024

Circulating extracellular microRNAs in the blood promote sociability in mice

Extracellular vesicles (EVs) are cell-derived small membrane vesicles and circulate throughout the body, but the impact of circulating EVs on brain function and behavior remains elusive. Here, we report that wild-type (WT) mouse blood, particularly EVs, increases sociability in socially impaired immunodeficient Rag1-/- mice, mimicking the effects of WT T cell transfer. These EVs localized to neurons and regulated PKC{varepsilon} expression, GABAA receptor synaptic localization, and inhibitory postsynaptic signaling in prefrontal cortex (PFC) pyramidal neurons. Injection of Rag1-/- EVs supplemented with miR-23a-3p and miR-103-3p enhanced synaptic function and sociability in Rag1-/- mice. T cells secreted miR-23a-3p via EVs, and Mir23a-/- T cells failed to increase sociability. Similar beneficial effects of WT blood EVs were observed in additional mouse models with sociability deficits, Cntnap2-/- and Shank3-/- mice. These findings uncover a previously unrecognized role of EV miRNAs in mediating immune modulation of synaptic function and social behavior, revealing a novel molecular pathway for immune-neuron communication.

neuroscience↗

bioRxiv2020

Cyclic-di-GMP induces STING-dependent ILC2 to ILC1 shift during innate type 2 lung inflammation

Type 2 inflammation is found in most forms of asthma, which may co-exist with recurrent viral infections, bacterial colonization, and host cell death. These processes drive the accumulation of intracellular cyclic-di-nucleotides such as cyclic-di-GMP (CDG). Group 2 innate lymphoid cells (ILC2s) are critical drivers of type 2 lung inflammation during fungal allergen exposure in mice; however, it is unclear how CDG regulates lung ILC responses during lung inflammation. Here, we show that CDG induced early airway type 1 interferon (IFN) production and dramatically suppressed both lung proliferating CD127+ST2+ ILC2s and Alternaria- and IL-33-induced lung inflammation. Further, transcriptomic analysis of CD127-ST2- Thy1.2+ ILCs, which were expanded and activated by CDG, revealed an ILC1 signature. CDG administration led to accumulation of IFN{gamma}+ and T-bet+ ILC1s, as well as neutrophilia, independent of IL-18R, IL-12, and STAT6 but dependent on stimulator of interferon genes (STING) and partially dependent on type 1 IFN signaling. Thus, CDG potently suppresses ILC2-driven lung inflammation and promotes ILC1 responses. These results suggest potential therapeutic modulation of STING to suppress type 2 inflammation and/or increase anti-viral responses during respiratory infections.

immunology↗