{"entity": "researcher", "timestamp": "2026-08-14T12:37:56.163Z", "family": "Broliden", "given": "Kristina", "initials": "K", "orcid": "0000-0003-2224-7664", "affiliations": ["Department of Medicine Solna, Division of Infectious Diseases, Karolinska Institutet, Department of Infectious Diseases, Karolinska University Hospital, Center for Molecular Medicine, Stockholm, Sweden."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/95346da4e5984d48bbb50032797155e5.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/95346da4e5984d48bbb50032797155e5"}}, "publications": [{"entity": "publication", "iuid": "626dde82bebd4d8bb7880ecc0a2237e0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/626dde82bebd4d8bb7880ecc0a2237e0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/626dde82bebd4d8bb7880ecc0a2237e0"}}, "title": "Spatial transcriptomics unveils estrogen-modulated immune responses and structural alterations in the ectocervical mucosa of depot medroxyprogesterone acetate users.", "authors": [{"family": "Kaldhusdal", "given": "Vilde", "initials": "V"}, {"family": "Boger", "given": "Mathias Franzen", "initials": "MF"}, {"family": "Tjernlund", "given": "Annelie", "initials": "A"}, {"family": "Burgener", "given": "Adam D", "initials": "AD"}, {"family": "Bradley", "given": "Frideborg", "initials": "F", "orcid": "0000-0003-3006-7284", "researcher": {"href": "https://publications.scilifelab.se/researcher/d51eaeb949e94bd39ab3605d495dc647.json"}}, {"family": "Lajoie", "given": "Julie", "initials": "J"}, {"family": "Omollo", "given": "Kenneth", "initials": "K"}, {"family": "Kimani", "given": "Joshua", "initials": "J"}, {"family": "Fowke", "given": "Keith", "initials": "K"}, {"family": "Czarnewski", "given": "Paulo", "initials": "P", "orcid": "0000-0001-8150-4021", "researcher": {"href": "https://publications.scilifelab.se/researcher/b84309de4e3946159c374ffa6d977560.json"}}, {"family": "Broliden", "given": "Kristina", "initials": "K", "orcid": "0000-0003-2224-7664", "researcher": {"href": "https://publications.scilifelab.se/researcher/95346da4e5984d48bbb50032797155e5.json"}}], "type": "journal article", "published": "2025-01-06", "journal": {"title": "Sci Rep", "issn": "2045-2322", "issn-l": "2045-2322", "volume": "15", "issue": "1", "pages": "1014"}, "abstract": "The injectable contraceptive, depot medroxyprogesterone acetate (DMPA), is associated with compromised cervical mucosal barriers. High-resolution spatial transcriptomics is applied here to reveal the spatial localization of these altered molecular markers. Ectocervical tissue samples from Kenyan sex workers using DMPA, or non-hormonal contraceptives, underwent spatial transcriptomics and gene set enrichment analyses. Integrated systemic estradiol levels and bulk tissue gene expression data from a larger cohort enhanced the study's scope. Unsupervised clustering unveiled four epithelial and seven submucosal layers, showcasing spatially restricted and diverse functional epithelial responses, and a less structured submucosal spatial ordering. DMPA associated with mucosal-wide immunoglobulin gene upregulation, verified by CD20+ B-cell immunostaining, and upregulated immune markers adjacent to the basal membrane. Downregulated genes represented spatially restricted disrupted epithelial barrier integrity and submucosal extracellular matrix dysfunction. The transcriptional profile was associated with markers of estrogen regulation. Collectively, our findings reveal estrogen-modulated distinct ectocervical transcriptional profiles associated with DMPA usage. While upregulation of immunoglobulin genes occurs throughout the mucosa, activation of innate immune responses and dysregulation of barrier integrity markers are spatially restricted. These results extend previous analyses using bulk transcriptomics and provide insights into the molecular landscape influenced by DMPA, shedding light on contraceptive effects and health implications.", "doi": "10.1038/s41598-024-83775-9", "pmid": "39762272", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "NGI Stockholm (Genomics Production)": "Service", "NGI Spatial omics": "Service", "NGI Stockholm (Genomics Applications)": "Service", "National Genomics Infrastructure": "Service", "NGI Short read": "Service", "Bioinformatics (NBIS)": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC11704007"}, {"db": "pii", "key": "10.1038/s41598-024-83775-9"}], "notes": [], "created": "2025-01-23T12:51:23.407Z", "modified": "2025-11-19T08:36:34.197Z"}, {"entity": "publication", "iuid": "c4b84ce2a57f40308f42f57e75b10952", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c4b84ce2a57f40308f42f57e75b10952.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c4b84ce2a57f40308f42f57e75b10952"}}, "title": "Vaginal candida infection is associated with host molecular signatures of neutrophil activation in the adjacent ectocervical mucosa in Kenyan sex workers", "authors": [{"family": "Hasselrot", "given": "Tyra", "initials": "T", "orcid": "0009-0002-5951-5618", "researcher": {"href": "https://publications.scilifelab.se/researcher/2b6969d7b33f4b1286c9dbea2fbaf79e.json"}}, {"family": "Boger", "given": "Mathias Franz\u00e9n", "initials": "MF"}, {"family": "Kaldhusdal", "given": "Vilde", "initials": "V"}, {"family": "\u00c5hlberg", "given": "Alexandra", "initials": "A"}, {"family": "Omollo", "given": "Kenneth", "initials": "K"}, {"family": "Lajoie", "given": "Julie", "initials": "J"}, {"family": "Kimani", "given": "Joshua", "initials": "J"}, {"family": "Tjernlund", "given": "Annelie", "initials": "A"}, {"family": "Fowke", "given": "Keith R", "initials": "KR"}, {"family": "Czarnewski", "given": "Paulo", "initials": "P", "orcid": "0000-0001-8150-4021", "researcher": {"href": "https://publications.scilifelab.se/researcher/b84309de4e3946159c374ffa6d977560.json"}}, {"family": "Broliden", "given": "Kristina", "initials": "K", "orcid": "0000-0003-2224-7664", "researcher": {"href": "https://publications.scilifelab.se/researcher/95346da4e5984d48bbb50032797155e5.json"}}], "type": "journal-article", "published": "2024-02-00", "journal": {"title": "American J Rep Immunol", "issn": "1046-7408", "issn-l": null, "volume": "91", "issue": "2", "pages": "e13814"}, "abstract": "Overgrowth of candida species in the human vaginal mucosa causes inflammation, which could render the mucosal barrier more susceptible to HIV infection. Here, we investigated whether this condition also affects the ectocervical mucosa, a potential site of HIV entry, in women at high risk of HIV infection.\n\nRetrospective medical data and ectocervical tissue samples were obtained from a cohort of Kenyan sex workers. Among 108 women, seven had signs of vaginal candida infection by wet smear microscopy and/or the presence of characteristic discharge. Women lacking these two criteria served as controls. Host transcriptomic profiling and quantitative in situ image analysis of epithelial barrier markers and CD4+ cell distribution were performed.\n\nThe candida group had 162 differentially expressed genes out of 15 435 genes as compared with the control group. Among these 162 genes, 147 were upregulated and 15 were downregulated. Gene expression pathway analysis indicated associations with an upregulated inflammatory response, defined primarily by markers of neutrophil activation. Transcription factor analysis revealed upregulation of pathways related to RELA/REL/NFKB1, JUN and STAT1 in the candida group. In situ image analysis of ectocervical tissue samples showed no differences between groups in terms of epithelial height, expression of epithelial junction proteins (E-cadherin, claudin-1, zonula occludens 1, and desmoglein-1), or epithelial CD4+ cell distribution.\n\nVaginal candida infection was associated with inflammation and neutrophil infiltration, but not with severe epithelial disruption or CD4+ cell infiltration, in the ectocervical mucosa.", "doi": "10.1111/aji.13814", "pmid": "40600913", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "BioImage Informatics": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11717577"}], "notes": [], "created": "2024-10-31T10:37:29.647Z", "modified": "2025-12-04T19:33:29.727Z"}, {"entity": "publication", "iuid": "a0a0ece375d24f3fafa2a00b725911ff", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a0a0ece375d24f3fafa2a00b725911ff.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a0a0ece375d24f3fafa2a00b725911ff"}}, "title": "Multi-omics analysis of the cervical epithelial integrity of women using depot medroxyprogesterone acetate.", "authors": [{"family": "Bradley", "given": "Frideborg", "initials": "F", "orcid": "0000-0003-3006-7284", "researcher": {"href": "https://publications.scilifelab.se/researcher/d51eaeb949e94bd39ab3605d495dc647.json"}}, {"family": "Franz\u00e9n Boger", "given": "Mathias", "initials": "M"}, {"family": "Kaldhusdal", "given": "Vilde", "initials": "V"}, {"family": "\u00c5hlberg", "given": "Alexandra", "initials": "A"}, {"family": "Edfeldt", "given": "Gabriella", "initials": "G"}, {"family": "Lajoie", "given": "Julie", "initials": "J"}, {"family": "Bergstr\u00f6m", "given": "Sofia", "initials": "S"}, {"family": "Omollo", "given": "Kenneth", "initials": "K"}, {"family": "Damdimopoulos", "given": "Anastasios", "initials": "A"}, {"family": "Czarnewski", "given": "Paulo", "initials": "P"}, {"family": "M\u00e5nberg", "given": "Anna", "initials": "A"}, {"family": "Oyugi", "given": "Julius", "initials": "J"}, {"family": "Kimani", "given": "Joshua", "initials": "J"}, {"family": "Nilsson", "given": "Peter", "initials": "P"}, {"family": "Fowke", "given": "Keith", "initials": "K"}, {"family": "Tjernlund", "given": "Annelie", "initials": "A"}, {"family": "Broliden", "given": "Kristina", "initials": "K", "orcid": "0000-0003-2224-7664", "researcher": {"href": "https://publications.scilifelab.se/researcher/95346da4e5984d48bbb50032797155e5.json"}}], "type": "journal article", "published": "2022-05-00", "journal": {"title": "PLoS Pathog.", "issn": "1553-7374", "volume": "18", "issue": "5", "pages": "e1010494", "issn-l": "1553-7366"}, "abstract": "Depot medroxyprogesterone acetate (DMPA) is an injectable hormonal contraceptive used by millions of women worldwide. However, experimental studies have associated DMPA use with genital epithelial barrier disruption and mucosal influx of human immunodeficiency virus (HIV) target cells. We explored the underlying molecular mechanisms of these findings. Ectocervical biopsies and cervicovaginal lavage (CVL) specimens were collected from HIV-seronegative Kenyan sex workers using DMPA (n = 32) or regularly cycling controls (n = 64). Tissue samples were assessed by RNA-sequencing and quantitative imaging analysis, whereas protein levels were measured in CVL samples. The results suggested a DMPA-associated upregulation of genes involved in immune regulation, including genes associated with cytokine-mediated signaling and neutrophil-mediated immunity. A transcription factor analysis further revealed DMPA-associated upregulation of RELA and NFKB1 which are involved in several immune activation pathways. Several genes significantly downregulated in the DMPA versus the control group were involved in epithelial structure and function, including genes encoding keratins, small proline-rich proteins, and cell-cell adhesion proteins. Pathway analyses indicated DMPA use was associated with immune activation and suppression of epithelium development, including keratinization and cornification processes. The cervicovaginal microbiome composition (Lactobacillus dominant and non-Lactobacillus dominant) had no overall interactional impact on the DMPA associated tissue gene expression. Imaging analysis verified that DMPA use was associated with an impaired epithelial layer as illustrated by staining for the selected epithelial junction proteins E-cadherin, desmoglein-1 and claudin-1. Additional staining for CD4+ cells revealed a more superficial location of these cells in the ectocervical epithelium of DMPA users versus controls. Altered protein levels of SERPINB1 and ITIH2 were further observed in the DMPA group. Identification of specific impaired epithelial barrier structures at the gene expression level, which were verified at the functional level by tissue imaging analysis, illustrates mechanisms by which DMPA adversely may affect the integrity of the genital mucosa.", "doi": "10.1371/journal.ppat.1010494", "pmid": "35533147", "labels": {"BioImage Informatics": "Service", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9119532"}, {"db": "pii", "key": "PPATHOGENS-D-21-02612"}], "notes": [], "created": "2022-08-30T13:46:44.982Z", "modified": "2022-12-07T11:49:48.217Z"}, {"entity": "publication", "iuid": "a29d11d5638d409ebe3b76aee7ec77b3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a29d11d5638d409ebe3b76aee7ec77b3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a29d11d5638d409ebe3b76aee7ec77b3"}}, "title": "Highly HIV-exposed HIV uninfected Kenyan female sex workers display a thick ectocervical epithelium", "authors": [{"family": "R\u00f6hl", "given": "Maria", "initials": "M"}, {"family": "Lajoie", "given": "Julie", "initials": "J"}, {"family": "Tjernlund", "given": "Annelie", "initials": "A"}, {"family": "Edfeldt", "given": "Gabriella", "initials": "G", "orcid": "0000-0003-0366-5588", "researcher": {"href": "https://publications.scilifelab.se/researcher/6538b950bbd440e3aa32435d23c98074.json"}}, {"family": "W\u00e4hlby", "given": "Carolina", "initials": "C", "orcid": "0000-0002-4139-7003", "researcher": {"href": "https://publications.scilifelab.se/researcher/c50194fbc8524d95b7152663ccf17f29.json"}}, {"family": "Boily-Larouche", "given": "Genevieve", "initials": "G"}, {"family": "Cheruiyot", "given": "Julianna", "initials": "J"}, {"family": "Kimani", "given": "Makubo", "initials": "M"}, {"family": "Kimani", "given": "Joshua", "initials": "J"}, {"family": "Oyugi", "given": "Julius", "initials": "J"}, {"family": "Fowke", "given": "Keith R.", "initials": "KR"}, {"family": "Broliden", "given": "Kristina", "initials": "K", "orcid": "0000-0003-2224-7664", "researcher": {"href": "https://publications.scilifelab.se/researcher/95346da4e5984d48bbb50032797155e5.json"}}], "type": null, "published": "2017-11-01", "journal": {"volume": null, "issn": null, "issue": null, "pages": null, "title": "HIV&Hepatitis Nordic Conference, Stockholm, 2017-09-27-29", "issn-l": null}, "abstract": "Background\r\nThe female genital tract is a critical site of HIV acquisition and a number of genetic and immunological correlates of relative resistance against infection have been described in the ectocervical mucosa. We hypothesize that a thick epithelium, a high concentration of epithelial junction proteins, together with a low concentration of HIV target cells (CCR5+CD4+T cells and dendritic cells) at a distant location is a beneficial combination that hinders sexual acquisition of HIV.\r\n\r\nMethods\r\nEctocervical biopsies were collected from female sex workers from Nairobi, Kenya, representing highly HIV-exposed but HIV seronegative who had been involved in sex work for 7 years or more (HESN) (n=29), HIV-infected (n=11), and uninfected individuals who were new to sex work (3 years or less) (n=39). Digital image analysis of immunofluorescent staining was used to identify genital mucosal factors affecting HIV susceptibility by characterizing the thickness and integrity as well as the spatial distribution of HIV target cells in the cervical epithelium.\r\n\r\nResults\r\nPreliminary results indicate that the HESN group display significantly thicker epithelium than the HIV+ group, and significantly lower numbers of potential HIV target cells than both the HIV+ group and those who were new to sex work.\r\n\r\nConclusion\r\nA deeper insight into what mucosal factors are affecting HIV susceptibility is of major importance to prevent sexual HIV transmission, and we hope to contribute to this needed knowledge.", "doi": null, "pmid": null, "labels": {"BioImage Informatics": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [], "notes": [], "created": "2017-11-01T11:47:33.003Z", "modified": "2025-11-17T09:52:46.049Z"}, {"entity": "publication", "iuid": "2625e25ccebf40388bfc4b5f0d0a6100", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2625e25ccebf40388bfc4b5f0d0a6100.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2625e25ccebf40388bfc4b5f0d0a6100"}}, "title": "Analysis of the Distribution of CD103 on CD8 T Cells in Blood and Genital Mucosa of HIVinfected Female Sex Workers", "authors": [{"family": "Gibbs", "given": "Anna", "initials": "A"}, {"family": "Buggert", "given": "Marcus", "initials": "M", "orcid": "0000-0003-0633-1719", "researcher": {"href": "https://publications.scilifelab.se/researcher/9a54e4b5136642eeafa77ac5118a0c81.json"}}, {"family": "Ranefall", "given": "Petter", "initials": "P", "orcid": "0000-0002-6699-4015", "researcher": {"href": "https://publications.scilifelab.se/researcher/4332883c0058421f8dfb85406ec03524.json"}}, {"family": "Introini", "given": "Andrea", "initials": "A"}, {"family": "Cheuk", "given": "Stanley", "initials": "S"}, {"family": "Eidsmo", "given": "Liv", "initials": "L", "orcid": "0000-0001-9237-8374", "researcher": {"href": "https://publications.scilifelab.se/researcher/57e083936a8144a19f0b2eb14dab6898.json"}}, {"family": "Hirbod", "given": "Taha", "initials": "T"}, {"family": "Ball", "given": "TerryB.", "initials": "T"}, {"family": "Kimani", "given": "Joshua", "initials": "J"}, {"family": "Kaul", "given": "Rupert", "initials": "R"}, {"family": "Karlsson", "given": "Annika C.", "initials": "AC"}, {"family": "W\u00e4hlby", "given": "Carolina", "initials": "C", "orcid": "0000-0002-4139-7003", "researcher": {"href": "https://publications.scilifelab.se/researcher/c50194fbc8524d95b7152663ccf17f29.json"}}, {"family": "Broliden", "given": "Kristina", "initials": "K", "orcid": "0000-0003-2224-7664", "researcher": {"href": "https://publications.scilifelab.se/researcher/95346da4e5984d48bbb50032797155e5.json"}}, {"family": "Tjernlund", "given": "Annelie", "initials": "A"}], "type": null, "published": "2016-10-17", "journal": {"volume": null, "issn": null, "issue": null, "pages": null, "title": "Conference on HIV Research for Prevention (HIV R4P), 2016, October 17\u201320, Chicago", "issn-l": null}, "abstract": "Background: Tissue resident memory (TRM) cells are characterized by the expression of several markers including \u03b1E(CD103)\u03b27 integrin and by their preferential localization in the epithelium of mucosal surfaces. However, little is known about the presence of TRM cells in the human female reproductive tract (FRT), and their eventual role in protecting the host against HIV infection therein. In this study, we compared the distribution of CD103, as a surrogate marker of tissue-residency, on CD8+ T cells between the FRT and blood of HIV-infected and uninfected women. \r\n\r\nMethods: Blood and ectocervical tissue biopsies were collected from HIV-seropositive (n = 19) and HIV-seronegative (n = 17) Kenyan female sex workers as well as HIV-seronegative lowerrisk women (n = 21). Flow cytometry was used to assess the phenotype of circulating CD103+ CD8+ T cells, while in situ staining with image analysis were performed to enumerate CD8+ CD103+ cells in ectocervical biopsies. \r\n\r\nResults: The HIV-infected women displayed a significantly lower proportion of circulating CD103+cells within CD8+ T cells as compared to uninfected women. Circulating CD103+CD8+ T cells from the HIV-infected women were highly activated and enriched within the effector memory pool. Similar to blood, the proportion of cervical CD103+ cells among CD8+ cells was significantly lower in the HIV-infected versus uninfected women, even though the absolute count of these cells was increased in the HIV-infected women. \r\n\r\nConclusions: Our data suggests that CD8+ T cells with the potential of residing within mucosal sites in virtue of their CD103 expression may be actively recruited to/or expanded in the FRT of chronically HIV-infected sex workers. This data poses the basis for further analysis of the phenotype and function of CD103+ CD8+ T cells residing in the FRT as TRM, and their eventual changes in the course of HIV infection.", "doi": null, "pmid": null, "labels": {"BioImage Informatics": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [], "notes": [], "created": "2017-11-01T12:02:48.993Z", "modified": "2025-11-17T09:52:26.023Z"}]}