Biology subjects

Goverman, J.

Publications and source records attributed to Goverman, J..

3 recordsLinked to original sources

bioRxiv2025

Th1 effector CD4 T cells rely on IFN-γ production to induce alopecia areata

Alopecia areata (AA) is an autoimmune disease that is clinically characterized by hair loss and histologically by a peribulbar infiltrate of CD8 and CD4 T cells. Prior studies have focused on the role of CD8 T cells in the development of AA; however, the role of CD4 T cells remains unclear. Here, we demonstrate that CD4 T cells from the skin draining lymph nodes (SDLN) of AA mice transferred disease into recipient mice. Further, these cells exhibited a T-helper type 1 (Th1) effector transcriptional and phenotypic profile. The pathogenic activity of these CD4 T cells was dependent upon the presence of endogenous CD8 T cells and host IFN-{gamma} responsiveness. Targeted deletion of CD4 T cell-mediated production of IFN-{gamma} abrogated the ability of this cell population to transfer disease. Together, these data provide mechanistic insights into pathways that lead to AA development, strengthening our understanding of the disease and inviting studies into exploring novel therapeutic strategies for human patients.

immunology↗

bioRxiv2024

Antimicrobial blue light-bathing therapy for wound infection control

The prevalence of antibiotic resistance and tolerance in wound infection management poses a serious and growing health threat, necessitating the exploration of alternative approaches. Antimicrobial blue light therapy offers an appealing, non-pharmacological solution. However, its practical application has been hindered by the requirement for high irradiance levels, which particularly raises safety concerns. Here, we introduce a light-bathing strategy that employs prolonged, continuous exposure to blue light at an irradiance range lower by more than an order of magnitude (5 mW/cm2). This method consistently applies bacteriostatic pressure, keeping wound bioburden low, all while minimizing photothermal risks. Leveraging tailor-made, wearable light-emitting patches, we conducted preclinical trials on rat models of wound infection, demonstrating its safety and efficacy for suppressing infections induced by methicillin- resistant S. aureus and multidrug-resistant P. aeruginosa. Our results pave a new way for the application of blue light therapy in wound care.

bioengineering↗

bioRxiv2018

Oligodendrocyte Precursor Cells Are Co-Opted by the Immune System to Cross-Present Antigen and Mediate Cytotoxicity

Oligodendrocyte precursor cells (OPCs) are abundant in the adult CNS and can be recruited to form new oligodendrocytes and myelin in response to injury or disease. However, in multiple sclerosis (MS), oligodendrocyte regeneration and remyelination are often incomplete, suggesting that recruitment and maturation of OPCs is impaired. MS and the rodent model experimental autoimmune encephalomyelitis (EAE) are characterized by infiltration of activated T-cells into the CNS. To investigate the mechanisms by which this neuroinflammatory process influences OPC mobilization, we performed in vivo fate tracing in an inflammatory demyelinating animal model. Results of our studies showed that the OPC differentiation and myelin production are inhibited by either adoptive transfer of CNS infiltrating cytokine producing effector T-cells or CNS production of interferon gamma (IFN{gamma}), using an astrocyte specific IFN{gamma} transgene model. In both systems, IFN{gamma} changes the profile of OPCs by inducing functional expression of the immunoproteasome and upregulation of MHC class I. OPCs exposed to IFN{gamma} are shown to cross present exogenous antigen to cytotoxic CD8 T-cells, which then produce proteases and FasL that results in subsequent caspase 3/7 activation and OPC death, both in vitro and in vivo. Cross presentation by OPCs is dependent on the cytosolic processing pathway and can be inhibited by small molecules targeting MHC class I antigen processing and the immunoproteasome subunits. Finally, the immunoproteasome subunit, PSMB8, is shown to be markedly increased on Sox10+ oligodendrocyte lineage cells only in the demyelinated white matter lesions from patients with MS. These findings support the notion that OPCs have multiple functions beyond differentiation into myelinating cells and adapt to their microenvironment by responding to local cues. In MS, OPCs may be co-opted by the immune system to perpetuate the autoimmune response. Strategies aimed at inhibiting the aberrant immune activation pathways in OPCs may allow more efficient remyelination in MS.

neuroscience↗