Circulating T Follicular Helper Subsets in Human Blood

Iwamoto, Yayoi; Ueno, Hideki

doi:10.1007/978-1-0716-1736-6_3

Cited by 5 publications

(4 citation statements)

References 9 publications

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“…Such Tfh cells also bear a canonical characteristic phenotype including CD40 ligand (CD40L), inducible T cell costimulator (ICOS), programmed death-1 (PD-1), and B and T lymphocyte attenuator (BTLA) [ 13 ]. In addition to the classical germinal center (GC) Tfh cells in secondary lymphoid organs, it has been increasingly appreciated that there is a small subset of analogous cells in human peripheral blood with “Tfh-like” characteristics, frequently termed as circulating Tfh (cTfh) cells [ 14 ]. Curiously, such Tfh-like cells share functional properties with Tfh cells but exhibit a greater capacity for IL-21 production and superior B cell helper capacity [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Circular RNA CircZNF644 Facilitates Circulating Follicular Helper T Cells Response in Patients with Graves’ Disease

Liu,

Wang,

et al. 2024

Journal of Immunology Research

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Aberrant accumulation of circulating follicular helper T cells (cTfh) has been found in the peripheral blood mononuclear cells (PBMCs) of Graves’ disease (GD) patients. However, the underlying mechanism that contributes to the imbalance of cTfh cells remains unknown. Previously, studies described a GD‐related circular RNAs (circRNAs)‐circZNF644 that might be associated with cTfh cells. This study aimed to investigate the role of circZNF644 on cTfh cells in GD patients. Here, we found that circZNF644 was highly stable expression in the PBMCs of GD patients, which was positively correlated with the serum levels of TSH receptor autoantibodies (TRAb). Knockdown of circZNF644 caused a reduction of the proportion of cTfh cells in vitro. Mechanistically, circZNF644 served as a ceRNA for miR‐29a‐3p to promote ICOS expression, resulting in increased cTfh cells. In the PBMCs of GD patients, circZNF644 expression was positively correlated with ICOS expression and the percentage of cTfh cells, but negatively related to miR‐29a‐3p expression. Additionally, a strong relationship between circZNF644 and IL‐21 was revealed in GD patients, and silencing of circZNF644 inhibited IL‐21 expression. Our study elucidated that elevated expression of circZNF644 is a key feature in the development of GD and may contribute to the pathogenic role of cTfh cells in GD.

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Section: Introductionmentioning

confidence: 99%

Circular RNA CircZNF644 Facilitates Circulating Follicular Helper T Cells Response in Patients with Graves’ Disease

Liu,

Wang,

et al. 2024

Journal of Immunology Research

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“…The expression of CXCR5 on T FH cells is associated with autoimmune disease progression [ 23 ] and serum levels of CXCR5 on T FH cells are associated with aggravated rheumatoid arthritis [ 24 ]. Data suggest that this chemokine receptor facilitates the ability of circulating T FH cells to rapidly extravagate passed the BBB into inflamed tissues [ 25 ] and serve as a core sentinel of dysregulated immunity in their target tissue [ 26 ]. Evidence of these T FH cells migrating into the inflamed brain after ischemic injury might play an important role in acute tissue damage, the formation of ectopic lymphoid structures, and subsequent long-term inflammation following stroke.…”

Section: Introductionmentioning

confidence: 99%

CXCL13 expressed on inflamed cerebral blood vessels recruit IL-21 producing TFH cells to damage neurons following stroke

Rayasam

Kijak

Kissel

et al. 2022

J Neuroinflammation

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Background Ischemic stroke is a leading cause of mortality worldwide, largely due to the inflammatory response to brain ischemia during post-stroke reperfusion. Despite ongoing intensive research, there have not been any clinically approved drugs targeting the inflammatory component to stroke. Preclinical studies have identified T cells as pro-inflammatory mediators of ischemic brain damage, yet mechanisms that regulate the infiltration and phenotype of these cells are lacking. Further understanding of how T cells migrate to the ischemic brain and facilitate neuronal death during brain ischemia can reveal novel targets for post-stroke intervention. Methods To identify the population of T cells that produce IL-21 and contribute to stroke, we performed transient middle cerebral artery occlusion (tMCAO) in mice and performed flow cytometry on brain tissue. We also utilized immunohistochemistry in both mouse and human brain sections to identify cell types and inflammatory mediators related to stroke-induced IL-21 signaling. To mechanistically demonstrate our findings, we employed pharmacological inhibitor anti-CXCL13 and performed histological analyses to evaluate its effects on brain infarct damage. Finally, to evaluate cellular mechanisms of stroke, we exposed mouse primary neurons to oxygen glucose deprivation (OGD) conditions with or without IL-21 and measured cell viability, caspase activity and JAK/STAT signaling. Results Flow cytometry on brains from mice following tMCAO identified a novel population of cells IL-21 producing CXCR5+ CD4+ ICOS-1+ T follicular helper cells (TFH) in the ischemic brain early after injury. We observed augmented expression of CXCL13 on inflamed brain vascular cells and demonstrated that inhibition of CXCL13 protects mice from tMCAO by restricting the migration and influence of IL-21 producing TFH cells in the ischemic brain. We also illustrate that neurons express IL-21R in the peri-infarct regions of both mice and human stroke tissue in vivo. Lastly, we found that IL-21 acts on mouse primary ischemic neurons to activate the JAK/STAT pathway and induce caspase 3/7-mediated apoptosis in vitro. Conclusion These findings identify a novel mechanism for how pro-inflammatory T cells are recruited to the ischemic brain to propagate stroke damage and provide a potential new therapeutic target for stroke.

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“…23 However, different T H subsets can also be distinguished based on their tendencies to migrate and localize to different tissues due to their differential expression of chemokine receptors such as CCR4, CCR6, and CXCR5. [24][25][26][27][28][29][30] Alterations in several of these T H subsets were demonstrated in elderly individuals. [13][14][15] Interestingly, recent studies also identified a novel B cell subset, termed ABCs (age-associated B cells), that expands with age and exhibits distinctive features from more classical B cell subsets like naïve B cells, class switched memory (CSM), and nonclass switched memory (NCSM) cells.…”

Section: Introductionmentioning

confidence: 99%

“…The ability of these T H subsets to produce different cytokine profiles is usually their key distinguishing feature, and the ability of T FH cells to help B cells is closely linked to their capacity to produce cytokines like interleukin‐21, which is primarily produced locally and is critical for humoral responses as well as the development of autoimmunity 23 . However, different T H subsets can also be distinguished based on their tendencies to migrate and localize to different tissues due to their differential expression of chemokine receptors such as CCR4, CCR6, and CXCR5 24–30 . Alterations in several of these T H subsets were demonstrated in elderly individuals 13–15 .…”

Section: Introductionmentioning

confidence: 99%

Adaptive immune responses in patients requiring revision after total knee arthroplasty

Jenkins

Phalke

Bell

et al. 2022

Journal Orthopaedic Research

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Dissatisfaction occurs in nearly 20% of patients after total knee arthroplasty (TKA); however, there remains only limited understanding of the biologic mechanisms that may contribute to suboptimal postoperative outcomes requiring revision surgery. Expansion of effector T and B cells, could promote an abnormal healing response via local or peripheral immune system mechanisms and contribute to inferior outcomes necessitating revision TKA. In this pilot study, we hypothesized that patients suffering from complications of arthrofibrosis or instability may exhibit differences in adaptive immune function. Patients (n = 31) undergoing revision TKA for an indication of arthrofibrosis or instability were prospectively enrolled. Whole blood and synovial fluid (SF) from the operative knee were collected at time of surgery. Peripheral blood mononuclear cells were isolated and analyzed by flow cytometry. Serum and SF were assessed for immunoglobulin levels by Luminex and antiphospholipid antibodies by enzyme‐linked immunoassay. No significant differences were observed in peripheral blood T/B cell populations or serum immunoglobulins levels between groups. SF analysis demonstrated significant differences between the two groups, with higher levels of immunoglobulin G1 (IgG1) (p = 0.0184), IgG3 (p = 0.0084) and antiphosphatidyl serine IgG (p = 0.034) in arthrofibrosis relative to instability patients. Increased levels of both IgG subclasses and antiphospholipid antibodies in the SF suggest that intra‐articular T‐B cell interactions, potentially triggered by exposure to apoptotic components generated during post‐op healing, could be functioning as a source of immune complexes that fuel fibrous tissue growth in arthrofibrotic patients.

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Circulating T Follicular Helper Subsets in Human Blood

Cited by 5 publications

References 9 publications

Circular RNA CircZNF644 Facilitates Circulating Follicular Helper T Cells Response in Patients with Graves’ Disease

Circular RNA CircZNF644 Facilitates Circulating Follicular Helper T Cells Response in Patients with Graves’ Disease

CXCL13 expressed on inflamed cerebral blood vessels recruit IL-21 producing TFH cells to damage neurons following stroke

Adaptive immune responses in patients requiring revision after total knee arthroplasty

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