Biology subjects

Eidsmo, L.

Publications and source records attributed to Eidsmo, L..

3 recordsLinked to original sources

bioRxiv2026

Tissue-resident memory T cells are diminished in the Kaposi sarcoma tumor microenvironment of people living with HIV

Kaposi sarcoma (KS) is a rare neoplasm and an AIDS-defining diagnosis in people living with HIV (PLWH). Although and chronic infection with Kaposi sarcoma-associated herpesvirus (KSHV) contributes to KS progression, the local immune mechanisms that are lost during tumor progression remain incompletely understood. Here, we systematically characterized global patterns in the KS tumor microenvironment (TME) in both PLWH and HIV-negative individuals. Spatial transcriptomics revealed distinct niches comprising of tumor cells, immune cells, and surrounding skin cells. Tumor regions expressed a characteristic endothelial-fibroblastic signature attributable to KS tumor cells (CD34, LYVE1, SCN9A), TME regions expressed marker genes for T cells, B cells and cancer-associated fibroblasts. Analysis of putative cell-cell interactions demonstrated that tumor cells preferentially interact with cells of the TME, including T cells, indicating an important role as hub of cellular communication in KS. Immunofluorescence imaging confirmed increased numbers of T cells, specifically tissue-resident memory T cells (TRM), in KS samples compared to healthy skin, accompanied by a pronounced upregulation of PD-1 expression that was predominantly localized to the TME. Notably, we identified HIV-associated alterations in the KS immune microenvironment: PLWH exhibited loss of CXCR3+ and IFN-gamma producing CD8+ TRM cells in the KS TME compared to HIV-negative patients, a finding consistent with impaired antitumor immunity. Together, our findings reveal HIV-associated disruption of functional anti-tumor immunity in the KS TME of PLWH. Increased PD-1 expression within T cells of the TME highlights potential therapeutic use of immune checkpoint inhibitors in KS.

immunology↗

bioRxiv2021

Single-cell analysis reveals MHCII expressing keratinocytes in pressure ulcers with worse healing outcomes

Pressure ulcer (PU) is a chronic wound often seen in spinal cord injury patients and other bed-bound individuals, particularly in the elderly population. Despite its association with high mortality, the pathophysiology of PU remains poorly understood. Here, we compared single-cell transcriptomic profiles of human epidermal cells from PU wound edges with those from uninjured skin and acute wounds (AWs) in healthy donors. We identified significant shifts in the cell composition and gene expression patterns in PU. In particular, we found that major histocompatibility complex class II (MHCII) expressing keratinocytes were enriched in patients with worse healing outcomes. Furthermore, we showed that the IFN{gamma} in PU-derived wound fluid could induce MHCII expression in keratinocytes and that these wound fluid-treated keratinocytes inhibited autologous T cell activation. In line with this observation, we found that T cells from PUs enriched with MHCII+ keratinocytes produced fewer inflammatory cytokines. Overall, our study provides a high-resolution molecular map of human PU compared to AW and intact skin, providing new insights into PU pathology and the future development of tailored wound therapy.

genomics↗

bioRxiv2021

Intestinal helminth infection transforms the CD4+ T cell composition of the skin

Intestinal helminth parasites can alter immune responses to vaccines, other infections, allergens and autoantigens, indicating effects on host immune responses in distal barrier tissues. We herein show that C57BL/6 mice infected with the strictly intestinal nematode Heligmosomoides polygyrus have impaired capacity to initiate skin immune responses and develop skin-resident memory cells to mycobacterial antigens, both during infection and months after deworming therapy. Surprisingly, and in contrast to a previously noted loss of T cells in peripheral lymph nodes, the skin of worm-infected mice harboured higher numbers of CD4+ T cells compared to skin of uninfected controls. H. polygyrus-specific TH2 cells accumulated during infection and remained after worm expulsion. Accumulation of TH2 cells in the skin was associated with increased expression of the skin-homing chemokine receptors CCR4 and CCR10 on CD4+ T cells in blood and mesenteric lymph nodes draining intestinal tissues, indicating gut-to-skin trafficking of cells. In conclusion, we show that infection by a strictly intestinal helminth has long-term effects on immune cell composition and local immune responses to unrelated antigens in the skin, revealing a novel mechanism for T cell colonization and worm-mediated immunosuppression in this organ.

immunology↗