T Follicular Helper Cell Subsets and the Associated Cytokine IL-21 in the Pathogenesis and Therapy of Asthma

Gong, Fang; Zheng, Ting; Zhou, Pengcheng

doi:10.3389/fimmu.2019.02918

Cited by 44 publications

(34 citation statements)

References 141 publications

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“…IL‐21, IL‐12, IL‐23 and TGF‐β are all required for development of Tfh cells, and IL‐21 plays a critical role in regulating Ig production and GC formation. It also acts in an autocrine fashion for Tfh cell development [64–66]. While IL‐21 is induced by IL‐6 through the STAT‐3 transcription factor, the mRNA for this cytokine showed minimal change with disease in young animals, but was significantly increased later in disease in the adult animals.…”

Section: Discussionmentioning

confidence: 99%

Gingival transcriptomics of follicular T cell footprints in progressing periodontitis

Ebersole

Kirakodu

Orraca

et al. 2021

Clinical and Experimental Immunology

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Summary Follicular helper T cells (Tfh) cells have been identified in the circulation and in tertiary lymphoid structures in chronic inflammation. Gingival tissues with periodontitis reflect chronic inflammation, so genomic footprints of Tfh cells should occur in these tissues and may differ related to aging effects. Macaca mulatta were used in a ligature‐induced periodontitis model [adult group (aged 12–23 years); young group (aged 3–7 years)]. Gingival tissue and subgingival microbiome samples were obtained at matched healthy ligature‐induced disease and clinical resolution sites. Microarray analysis examined Tfh genes (n = 54) related to microbiome characteristics documented using 16S MiSeq. An increase in the major transcription factor of Tfh cells, BCL6, was found with disease in both adult and young animals, while master transcription markers of other T cell subsets were either decreased or showed minimal change. Multiple Tfh‐related genes, including surface receptors and transcription factors, were also significantly increased during disease. Specific microbiome patterns were significantly associated with profiles indicative of an increased presence/function of Tfh cells. Importantly, unique microbial complexes showed distinctive patterns of interaction with Tfh genes differing in health and disease and with the age of the animals. An increase in Tfh cell responsiveness occurred in the progression of periodontitis, affected by age and related to specific microbial complexes in the oral microbiome. The capacity of gingival Tfh cells to contribute to localized B cell activation and active antibody responses, including affinity maturation, may be critical for controlling periodontal lesions and contributing to limiting and/or resolving the lesions.

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Section: Discussionmentioning

confidence: 99%

Gingival transcriptomics of follicular T cell footprints in progressing periodontitis

Ebersole

Kirakodu

Orraca

et al. 2021

Clinical and Experimental Immunology

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“…Although less characterized, majority of peripheral antigen specific CD4 + T cells that were shown to correlate with antibody production in COVID-19 convalescent individuals may represent cTFH cells (4,6). cTFH cells can be further defined as central memory like or effector memory like based on the expression of CCR7 and PD-1 (28)(29)(30). In particular, CCR7 lo PD-1 + effector memory like cTFH cells in the peripheral circulation can indicate the bona fide TFH cell activity and foster antibody response against re-exposure of antigen (29).…”

Section: Introductionmentioning

confidence: 99%

Peripheral CD4+ T cell subsets and antibody response in COVID-19 convalescent individuals

Gong¹,

Dai²,

Zheng³

et al. 2020

Journal of Clinical Investigation

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149

159

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Background: Marked progress is achieved in understanding the physiopathology of COVID-19 that caused global pandemics. However, CD4 + T cell population that is critical for antibody response in COVID-19 is poorly understood. Methods: In this study, we provided a comprehensive analysis of peripheral CD4 + T cells of 13 COVID-19 convalescent patients, as defined as confirmed free of SARS-CoV-2 for 2-4 weeks, using flow cytometry, magnetic chemiluminescence enzyme antibody immunoassay and correlated the data with clinical characteristics. Results: We observed that relative to healthy individuals, convalescent patients displayed an altered peripheral CD4 + T cell spectrum. Specifically, consistent with other viral infections, cTFH1 cell associated with SARS-CoV-2 targeting antibodies, which was found to skew with disease severity as more severe individuals showed higher frequency of TEM and TFH-EM cells but a lower frequency of TCM, TFH-CM and TNaive cells, relative to mild and moderate patients. Interestingly, higher frequency of cTFH-EM cells correlated with lower number of recorded admission blood oxygen level in convalescent patients. These observations might constitute residual effects by which COVID-19 can impact the homeostasis of CD4 + T cells in the long-term and explain the highest ratio of classswitched virus-specific antibody producing individuals found in our severe COVID-19 cohort. Conclusion: Together, our study demonstrated close connection between CD4 + T cells and antibody production in COVID-19 convalescents.

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“…ICOS expression is associated with IL-4 production 31 and Th2 responses 32 in the lung and lymph nodes during asthma 33 . Moreover, ICOS is highly expressed on T follicular helper (Tfh) cells important for driving B cell class switching to IgE [34][35][36] , suggesting that P. kudriavzevii-exposed mice demonstrate increased adaptive immunity-driven lung inflammation. P. kudriavzevii-exposed animals also demonstrated an increase in the proportion and numbers of Th17 cells in the lung, identified by RORt high expression and IL-17 secretion (Figure 2G-H), and greater numbers of lung GATA3+ Th2 cells (Figure 2I).…”

mentioning

confidence: 99%

Bacterial–fungal interactions in the neonatal gut influence asthma outcomes later in life

Boutin

Petersen

Woodward

et al. 2021

eLife

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Bacterial members of the infant gut microbiota and bacterial-derived short-chain fatty acids (SCFAs) have been shown to be protective against childhood asthma, but a role for the fungal microbiota in asthma etiology remains poorly defined. We recently reported an association between overgrowth of the yeast Pichia kudriavzevii in the gut microbiota of Ecuadorian infants and increased asthma risk. In the present study, we replicated these findings in Canadian infants and investigated a causal association between early life gut fungal dysbiosis and later allergic airway disease (AAD). In a mouse model, we demonstrate that overgrowth of P. kudriavzevii within the neonatal gut exacerbates features of type-2 and -17 inflammation during AAD later in life. We further show that P. kudriavzevii growth and adherence to gut epithelial cells are altered by SCFAs. Collectively, our results underscore the potential for leveraging inter-kingdom interactions when designing putative microbiota-based asthma therapeutics.

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T Follicular Helper Cell Subsets and the Associated Cytokine IL-21 in the Pathogenesis and Therapy of Asthma

Cited by 44 publications

References 141 publications

Gingival transcriptomics of follicular T cell footprints in progressing periodontitis

Gingival transcriptomics of follicular T cell footprints in progressing periodontitis

Peripheral CD4+ T cell subsets and antibody response in COVID-19 convalescent individuals

Bacterial–fungal interactions in the neonatal gut influence asthma outcomes later in life

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