Role of the CXCL13/CXCR5 Axis in Autoimmune Diseases

Pan, Zijian; Zhu, Tong; Liu, Yanjun; Zhang, Nannan

doi:10.3389/fimmu.2022.850998

Cited by 53 publications

(41 citation statements)

References 198 publications

(315 reference statements)

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“…In our study, the selected patients were all newly diagnosed IBD patients at the early stage of the disease. In addition, CD4+CXCR5+ T cells included not only CD4+CXCR5+Foxp3- T follicular helper (Tfh) cells, but also CD4+CXCR5+Foxp3+ T follicular regulator (Tfr) cells ( 24 , 25 ). Furthermore, Cxcl13 -/- knockout mice were used to construct DSS-induced colitis model to verify the role of CXCL13 in IBD.…”

Section: Discussionmentioning

confidence: 99%

CXCL13 is elevated in inflammatory bowel disease in mice and humans and is implicated in disease pathogenesis

Liu

et al. 2022

Front. Immunol.

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CXCL13 is a chemokine that is widely involved in the pathogenesis of autoimmune diseases, tumors and inflammatory diseases. In this study, we investigate the role of CXCL13 in the pathogenesis of inflammatory bowel disease using both clinical specimens and animal models. We found that the serum CXCL13 concentration in IBD patients was significantly higher than that in healthy controls, and correlated with that of CRP, neutrophils counts and hemoglobin. The increase of CXCL13 in IBD patients might be related to the significant decrease of circulating CD4+CXCR5+ T cells, the increase of CD19+CD5+ B cells and the enhancement of humoral immunity. In mice colitis model, we also found elevated levels of CXCL13 in colon tissue. Cxcl13-/- knockout mice exhibited a mild, self-limiting form of disease. Additionally, CXCL13 deficiency restricted CD4+CXCR5+ T cells migration in mesenteric lymph nodes, resulting locally regulatory B cells increased in colon. In conclusion, our findings raise the possibility that CXCL13 plays a critical role in the pathogenesis of IBD. We believe that our findings will contribute to the understanding of the etiology, and that antagonizing or inhibiting CXCL13 may work as a potential adjunctive therapy strategy for patients with IBD.

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Section: Discussionmentioning

confidence: 99%

CXCL13 is elevated in inflammatory bowel disease in mice and humans and is implicated in disease pathogenesis

Liu

et al. 2022

Front. Immunol.

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“…This brings us to CXCL13 as a soluble part of the CXCL13/CXCR5 immune axis, which is, as is the case for cTfh cells, physiologically detectable in blood and increased upon immune activation in the same contexts of infection, vaccination, and autoimmune disorders [ 34 , 75 , 76 ]. Plasma CXCL13 elevations, contrary to their cellular counterparts, are neither antigen- nor disease-specific.…”

Section: The Cxcl13/cxcr5 Immune Axis In the Peripheral Immune Systemmentioning

confidence: 99%

“…With regard to autoimmunity, CXCL13 elevations in the blood occur in SLE, RA, SS, MS, and MG, and are proposed biomarkers for disease activity, treatment response, and treatment targets for autoimmune disorders [ 30 , 34 , 80 , 81 , 82 ]. Preclinical therapeutic intervention studies with an anti-CXCL13 monoclonal antibody accordingly showed comparable effectiveness compared to standard treatments in mouse models of RA (collagen-induced arthritis) and MS (experimental autoimmune encephalomyelitis) [ 82 ].…”

Section: The Cxcl13/cxcr5 Immune Axis In the Peripheral Immune Systemmentioning

confidence: 99%

“…Accumulating evidence revealing heterogeneities in subset differentiation and frequency distributions, and linking the activation states of certain subsets to antigen-specific high-affinity antibody responses, have made them hot topics in infection, vaccination, autoimmunity, and cancer research [ 19 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. Furthermore, CXCL13/CXCR5-associated immune activities occur in non-lymphoid tissues, where they contribute to organizing and shaping in situ adaptive immune responses via the formation of ELS [ 30 , 31 ] at chronic inflammatory sites during persistent infections, autoimmune diseases, and cancer [ 2 , 31 , 32 , 33 , 34 , 35 ].…”

Section: Introductionmentioning

confidence: 99%

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The CXCL13/CXCR5 Immune Axis in Health and Disease—Implications for Intrathecal B Cell Activities in Neuroinflammation

Harrer

Otto

Radlberger

et al. 2022

Cells

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The chemokine C-X-C- ligand 13 (CXCL13) is a major B cell chemoattractant to B cell follicles in secondary lymphoid organs (SLO) that proposedly recruits B cells to the cerebrospinal fluid (CSF) during neuroinflammation. CXCR5, the cognate receptor of CXCL13, is expressed on B cells and certain T cell subsets, in particular T follicular helper cells (Tfh cells), enabling them to follow CXCL13 gradients towards B cell follicles for spatial proximity, a prerequisite for productive T cell–B cell interaction. Tfh cells are essential contributors to B cell proliferation, differentiation, and high-affinity antibody synthesis and are required for germinal center formation and maintenance. Circulating Tfh cells (cTfh) have been observed in the peripheral blood and CSF. Furthermore, CXCL13/CXCR5-associated immune activities organize and shape adaptive B cell-related immune responses outside of SLO via the formation of ectopic lymphoid structures in inflamed tissues, including the central nervous system (CNS). This review summarizes the recent advances in our understanding of the CXCL13/CXCR5 immune axis and its role in vaccination, autoimmunity, and infection with a special focus on its relevance for intrathecal B cell activities in inflammatory CNS diseases.

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“…The copyright holder for this this version posted December 14, 2022. ; https://doi.org/10.1101/2022.12.13.22283427 doi: medRxiv preprint autoimmune diseases (Pan et al 2022) and hematologic cancers (Hussain et al 2013). Due to its plethora of activities and effects upon several cell types, CXCL13 can be regarded as a biomarker of both lymphoid (humoral and cellular) and myeloid cell activation and networking.…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal fluid CXCL13 identifies a subgroup of people living with HIV with prominent intrathecal synthesis, immune activation, and neurocognitive impairment regardless of effective antiretroviral therapy

Trunfio

Mighetto

Napoli

et al. 2022

Preprint

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Background: Plasma C-X-C-motif chemokine ligand-13 (CXCL13) has been linked to disease progression and mortality in people living with HIV (PLWH) and is a candidate target for immune-based strategies for HIV cure. Its role in central nervous system (CNS) of PLWH has not been detailed. We described CSF CXCL13 levels and its potential associations with neurological outcomes. Methods: Cross-sectional study enrolling PLWH without confounding for CXCL13 production. Subjects were divided according to CSF HIV-RNA in controllers (<20 cp/mL) and viremics. CSF CXCL13, and biomarkers of blood-brain barrier (BBB) impairment, intrathecal synthesis, and immune activation were measured by commercial immunoturbidimetric and ELISA assays. All subjects underwent neurocognitive assessment. Sensitivity analyses were conducted in subjects with intact BBB only. Results: 175 subjects were included. Prevalence of detectable CSF CXCL13 was higher in viremics (31.4%) compared to controllers (13.5%; OR 2.9 [1.4-6.3], p=0.006), but median CSF levels did not change (15.8 [8.2-91.0] vs 10.0 [8.1-14.2] pg/mL). In viremics (n=86), CXCL13 associated with higher CSF HIV-RNA, proteins, neopterin, Tourtelotte index, and CSF-to-serum albumin ratio. In controllers (n=89), CXCL13 associated with higher CD4+T-cells count, CD4/CD8 ratio, CSF proteins, neopterin, and several intrathecal synthesis markers. Detection of CSF CXCL13 in controllers increased the likelihood of HIV-associated neurocognitive disorders (58.3% vs 28.6%, p=0.041) and HIV-related CNS disorders (8.3% vs 0%, p=0.011). Sensitivity analyses confirmed all these findings. Conclusions: CSF CXCL13 identified a subgroup of PLWH presenting increased CNS IgG synthesis, and immune activation. In controllers, CSF CXCL13 associated with increased likelihood of neurocognitive impairment and HIV-related CNS disorders.

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Role of the CXCL13/CXCR5 Axis in Autoimmune Diseases

Cited by 53 publications

References 198 publications

CXCL13 is elevated in inflammatory bowel disease in mice and humans and is implicated in disease pathogenesis

CXCL13 is elevated in inflammatory bowel disease in mice and humans and is implicated in disease pathogenesis

The CXCL13/CXCR5 Immune Axis in Health and Disease—Implications for Intrathecal B Cell Activities in Neuroinflammation

Cerebrospinal fluid CXCL13 identifies a subgroup of people living with HIV with prominent intrathecal synthesis, immune activation, and neurocognitive impairment regardless of effective antiretroviral therapy

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