Biology subjects

Makinde, H. M.

Publications and source records attributed to Makinde, H. M..

4 recordsLinked to original sources

bioRxiv2025

Cellular composition of tissue-resident monocyte-lineage cells reveal functional heterogeneity during inflammatory arthritis

Tissue-resident monocyte-lineage cell (TRMC) are an extravascular population distinct from circulating monocytes and synovial macrophages and are critical for the development of inflammatory arthritis. However, the precise identities and origins of TRMC subpopulations remain unclear. Here, we characterize the ontogeny of TRMC, which are comprised of bone-marrow (BM)-derived and an embryonic, long-lived population. Furthermore, we identified three TRMC subpopulations, distinguished by expression of TIM4, CX3CR1, and MHCII. Clodronate-laden liposome reduces the number of TRMC but does not impact the proportions or transcriptional profile of TRMC subpopulations at 7 days post administration. TIM4+CX3CR1+ and TIM4+ TRMC represent long-lived population, whereas MHCII+ TRMC are BM-derived and dependent on Ccr2 during steady state. BM-derived TRMC expand and replenish the TIM4+CX3CR1+ and TIM4+ TRMC compartments throughout the peak and plateau of inflammatory arthritis. These findings underscore the importance heterogeneity within TRMC and highlight their distinct responses to synovial disruption and potential roles in rheumatoid arthritis (RA).

immunology↗

bioRxiv2021

Tissue-resident, extravascular CD64-Ly6C- population forms a critical barrier for inflammation in the synovium

Monocytes are one of the most abundant immune cells infiltrating the inflamed organs. However, the majority of studies on monocytes focus on circulating cells, rather than those in the tissue. Here, we identify and characterize an intravascular (i.v.) and extravascular (e.v.) synovial population (Syn Ly6C- cells) which lack cell surface markers of classical monocytes (Ly6C and CD62) or tissue macrophages (CD64 and Tim4), are transcriptionally distinct and conserved in RA patients. e.v. Syn Ly6C- cells are independent of NR4A1 and CCR2, long-lived and embryonically derived while the i.v. Syn Ly6C- cells are dependent on NR4A1, short lived and derived from circulating NCM. e.v. Syn Ly6C- cells undergo increased proliferation and reverse diapedesis dependent on LFA1 in response to arthrogenic stimuli and are required for the development of RA-like disease. These findings uncover a new facet of mononuclear cell biology and are imperative to understanding tissue-resident myeloid cell function in RA.

immunology↗

bioRxiv2018

Traumatic brain injury-associated microglia adopt longitudinal transcriptional changes consistent with long-term depression of synaptic strength

Traumatic brain injury (TBI) is an under-recognized public health threat. Even mild brain injury, or concussions, may lead to long-term neurologic impairment. Microglia play a fundamental role in the development and progression of this subsequent neurologic impairment. Despite this, a microglia-specific injury signature has yet to be identified. In the current study we hypothesized that TBI-associated microglia would adopt longitudinal changes in their transcriptional profile associated with pathways linked to the development of motor, cognitive, and behavioral disorders. C57BL/6 mice underwent TBI via a controlled cortical impact and were followed longitudinally. FACSorted microglia from TBI mice were subjected to RNA-sequencing at 7, 30, and 90 days post-injury. We identified 4 major patterns of gene expression corresponding to the host defense response, synaptic potentiation, lipid remodeling, and membrane polarization. In particular, significant upregulation of genes involved in long-term synaptic potentiation including Ptpn5, Shank3, and Sqstm1 were observed offering new insight into a previously unknown role of microglia in the weakening of synaptic efficacy between neurons after brain injury.

neuroscience↗

bioRxiv2018

Monocyte depletion attenuates the development of posttraumatic hydrocephalus and preserves white matter integrity after traumatic brain injury

Monocytes are amongst the first cells recruited into the brain after traumatic brain injury (TBI). We have shown monocyte depletion 24 hours prior to TBI reduces brain edema, decreases neutrophil infiltration and improves behavioral outcomes. Additionally, both lesion and ventricle size correlate with poor neurologic outcome after TBI. Therefore, we aimed to determine the association between monocyte infiltration, lesion size, and ventricle volume. We hypothesized that monocyte depletion would attenuate lesion size, decrease ventricle enlargement, and preserve white matter in mice after TBI. C57BL/6 mice underwent pan monocyte depletion via intravenous injection of liposome-encapsulated clodronate. Control mice were injected with liposome-encapsulated PBS. TBI was induced via an open-head, controlled cortical impact. Mice were imaged using magnetic resonance imaging (MRI) at 1, 7, and 14 days post-injury to evaluate progression of lesion and to detect morphological changes associated with injury (3D T1- weighted MRI) including regional alterations in white matter patterns (multi-direction diffusion MRI). Lesion size and ventricle volume were measured using semi-automatic segmentation and active contour methods with the software program ITK-SNAP. Data was analyzed with the statistical software program PRISM. No significant effect of monocyte depletion on lesion size was detected using MRI following TBI (p=0.4). However, progressive ventricle enlargement following TBI was observed to be attenuated in the monocyte-depleted cohort (5.3 {+/-} 0.9mm3) as compared to the sham-depleted cohort (13.2 {+/-} 3.1mm3; p=0.02). Global white matter integrity and regional patterns were evaluated and quantified for each mouse after extracting fractional anisotropy maps from the multi-direction diffusion-MRI data using Siemens Syngo DTI analysis package. Fractional anisotropy values were preserved in the monocyte-depleted cohort (123.0 {+/-} 4.4mm3) as compared to sham-depleted mice (94.9 {+/-} 4.6mm3; p=0.025) by 14 days post-TBI. The MRI derived data suggests that monocyte depletion at the time of injury may be a novel therapeutic strategy in the treatment of TBI. Furthermore, non-invasive longitudinal imaging allows for the evaluation of both TBI progression as well as therapeutic response over the course of injury.

neuroscience↗