Cellular and molecular determinants mediating the dysregulated germinal center immune dynamics in systemic lupus erythematosus Article Swipe
Spiros Georgakis
,
Kalliopi Ioannidou
,
Bernat Bramon Mora
,
Michail Orfanakis
,
Cloé Brenna
,
Yannick D. Müller
,
Perla M. Del Río Estrada
,
Ashish Sharma
,
Giuseppe Pantaleo
,
Laurence de Leval
,
Denis Comte
,
Raphaël Gottardo
,
Constantinos Petrovas
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.3389/fimmu.2025.1530327
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.3389/fimmu.2025.1530327
Introduction Systemic lupus erythematosus (SLE) is characterized by dysregulated humoral immunity, leading to the generation of autoreactive B cells that can differentiate both within and outside of lymph node (LN) follicles. Methods Here, we employed spatial transcriptomics and multiplex imaging to investigate the follicular immune landscaping and the in situ transcriptomic profile in LNs from SLE individuals. Results Our spatial transcriptomic analysis revealed robust type I IFN and plasma cell signatures in SLE compared to reactive, control follicles. Cell deconvolution revealed that follicular T cell subsets are mainly affected by the type I IFN fingerprint of SLE follicles. Dysregulation of T FH differentiation was documented by i) the significant reduction of Bcl6 hi T FH cells, ii) the reduced cell density of potential IL-4 producing T FH cell subsets associated with the impaired transcriptomic signature of follicular IL-4 signaling and iii) the loss of their correlation with GC-B cells. This profile was accompanied by a marked reduction of Bcl6 hi B cells and an enrichment of extrafollicular CD19 hi CD11c hi Tbet hi , age-associated B cells (ABCs), known for their autoreactive potential. The increased prevalence of follicular IL-21 hi cells further reveals a hyperactive microenvironment in SLE compared to control. Discussion Taken together, our findings highlight the altered immunological landscape of SLE follicles, likely fueled by potent inflammatory signals such as sustained type I IFN and/or IL-21 signaling. Our work provides novel insights into the spatial molecular and cellular signatures of SLE follicular B and T FH cell dynamics, and points to druggable targets to restore immune tolerance and enhance vaccine responses in SLE patients.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3389/fimmu.2025.1530327
- OA Status
- gold
- Cited By
- 2
- References
- 110
- Related Works
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- OpenAlex ID
- https://openalex.org/W4407554407
All OpenAlex metadata
Raw OpenAlex JSON
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https://openalex.org/W4407554407Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.3389/fimmu.2025.1530327Digital Object Identifier
- Title
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Cellular and molecular determinants mediating the dysregulated germinal center immune dynamics in systemic lupus erythematosusWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-02-13Full publication date if available
- Authors
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Spiros Georgakis, Kalliopi Ioannidou, Bernat Bramon Mora, Michail Orfanakis, Cloé Brenna, Yannick D. Müller, Perla M. Del Río Estrada, Ashish Sharma, Giuseppe Pantaleo, Laurence de Leval, Denis Comte, Raphaël Gottardo, Constantinos PetrovasList of authors in order
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https://doi.org/10.3389/fimmu.2025.1530327Publisher landing page
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://doi.org/10.3389/fimmu.2025.1530327Direct OA link when available
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Germinal center, Immune system, Immunology, Medicine, Systemic disease, Immunopathology, Antibody, B cellTop concepts (fields/topics) attached by OpenAlex
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2Total citation count in OpenAlex
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2025: 2Per-year citation counts (last 5 years)
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110Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| primary_location.raw_source_name | Frontiers in Immunology |
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| publication_date | 2025-02-13 |
| publication_year | 2025 |
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