scholarly journals Critical Roles of Balanced T Helper 9 Cells and Regulatory T Cells in Allergic Airway Inflammation and Tumor Immunity

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Muhua Huang ◽  
Jingcheng Dong
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Airway Inflammation ◽  
Tumor Immunity ◽  
Allergic Airway Inflammation ◽  
Treg Cells ◽  
T Helper ◽  
Th Cells ◽  
Th9 Cells ◽  
And Function

CD4+T helper (Th) cells are important mediators of immune responses in asthma and cancer. When counteracted by different classes of pathogens, naïve CD4+T cells undergo programmed differentiation into distinct types of Th cells. Th cells orchestrate antigen-specific immune responses upon their clonal T-cell receptor (TCR) interaction with the appropriate peptide antigen presented on MHC class II molecules expressed by antigen-presenting cells (APCs). T helper 9 (Th9) cells and regulatory T (Treg) cells and their corresponding cytokines have critical roles in tumor and allergic immunity. In the context of asthma and cancer, the dynamic internal microenvironment, along with chronic inflammatory stimuli, influences development, differentiation, and function of Th9 cells and Treg cells. Furthermore, the dysregulation of the balance between Th9 cells and Treg cells might trigger aberrant immune responses, resulting in development and exacerbation of asthma and cancer. In this review, the development, differentiation, and function of Th9 cells and Treg cells, which are synergistically regulated by various factors including cytokine signals, transcriptional factors (TFs), costimulatory signals, microenvironment cues, metabolic pathways, and different signal pathways, will be discussed. In addition, we focus on the recent progress that has helped to achieve a better understanding of the roles of Th9 cells and Treg cells in allergic airway inflammation and tumor immunity. We also discuss how various factors moderate their responses in asthma and cancer. Finally, we summarize the recent findings regarding potential mechanisms for regulating the balance between Th9 and Treg cells in asthma and cancer. These advances provide opportunities for novel therapeutic strategies that are aimed at reestablishing the balance of these cells in the diseases.

scholarly journals Immunostimulation During and After R-CHOP Therapy for B-Cell Lymphoma

2016 ◽  
Vol 01 (01) ◽  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Tumor Immunity ◽  
Cd8 T Cells ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Treg Cells ◽  
T Cell Subsets ◽  
T Helper ◽  
Chop Therapy

Backgrounds: Many studies show an immune imbalance in the tumor environment; some reports show that the T helper 1 (Th1)/ T helper 2 (Th2) ratio, the number of regulatory T-cells (Treg cells) or CD8+T-cells, and the CD8+Tcell/Treg cell ratio are associated with tumor suppression and expansion. Additionally, chemotherapy was reported to affect the immunity of patients with malignancy. Patients and Methods: Using flow cytometry we measured peripheral blood lymphocytes including non T-cells, as well as T-cell subsets such as CD3+T-cells, CD4+T-cells, CD8+T-cells, Treg cells, Th1 cells and Th2 cells before treatment, at the fourth cycle, and at 1, 3, 6 and 12 months after treatment in 21 patients with B-cell lymphoma receiving R-CHOP therapy. We also analyzed the changes in three immune indexes that reflect anti-tumor immunity (the CD4/CD8 ratio, the CD8/Treg ratio and the Th1/Th2 ratio). Results: Compared to pre-treatment there were significant decreases in the CD4/CD8 ratio between 1 month and 12 months after treatment (p<0.001, for all time points). The CD8/Treg ratio gradually increased with treatment with significant increases observed at 6 months (p=0.009) and 12 months after treatment (p=0.002). The Th1/ Th2 ratio showed a significant increase only before 4 cycles of therapy (p=0.007). Conclusion: Based on the changes in these three immune indexes, we propose that anti-tumor immunity improved after R-CHOP therapy, which enhanced the efficacy of R-CHOP therapy for lymphoma as well as its direct cytotoxic activity

scholarly journals Impact of T Helper Cell Subtype on CAR-T Cell Therapy Efficacy

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Ibrahim M. Khan, BS BA ◽  
Andrew S. Nelson, PhD ◽  
Mark H. Kaplan, PhD
Keyword(s):  
T Cells ◽  
B Cell ◽  
Culture Conditions ◽  
Cell Killing ◽  
T Helper ◽  
Th Cells ◽  
Car T Cells ◽  
Th9 Cells ◽  
Tnf Α ◽  
Car T

Background and Hypothesis: Chimeric antigen receptors (CARs) are recombinant receptors with high affinity for the target antigen. Used for tumor therapy, CARs are transduced into patient T cells. CAR-T cells specific for CD19 are used to treat B cell acute lymphoblastic leukemia (B-ALL). Cancerous B cells are destroyed by CAR-T cells in an antigen-specific manner. Currently being used in conjunction with radiation and other cancer therapies to prohibit relapse, Dr. Marco Davila of the Moffitt Cancer Center, has shown that CAR-T therapy induces long term remission and B cell aplasia. Experimental Design: In this experiment the CAR vector obtained from Dr. Davila was transduced into T helper cells cultured under varying conditions (Th0, Th9, and ThGranzyme A). B cell killing and longevity of transduced CAR-Th cells were monitored as part of the criteria for determining the most effective Th subtype for the CAR-T therapy. The target cell killing-mechanism was analyzed at the RNA level using quantitative polymerase chain reaction (qPCR) to analyze gene expression of cytotoxic molecules including granzymes A/B, perforins, Fas-FasL, and TNF-α. Th9 cells were expected to be among the most effective of the indicated subtypes due to their longevity and coordination of the immune response. Results: T cells in all conditions were effectively transduced for CAR expression, although Th9 cells demonstrated a greater proportion of cultured cells that were transduced with the CAR. QPCR results suggest that there is specification of cytotoxic programs among the culture conditions. In Th9 cells, qPCR results suggest their use of perforin and TNF-α. Ongoing studies will compare cytotoxic activity. Potential Impact: Further steps after determining the most effective culture conditions include injecting transduced Th cells of the optimized subtype into mice afflicted with BALL to assess cancer killing in vivo as well as the potential harm of the therapy to the patient.

scholarly journals Modulation of Tetraspanin 32 (TSPAN32) Expression in T Cell-Mediated Immune Responses and in Multiple Sclerosis

2019 ◽  
Vol 20 (18) ◽  
pp. 4323 ◽  
Author(s):  
Salvo Danilo Lombardo ◽  
Emanuela Mazzon ◽  
Maria Sofia Basile ◽  
Giorgia Campo ◽  
Federica Corsico ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Cancer Metastasis ◽  
Treg Cells ◽  
T Helper ◽  
Autoimmune Encephalomyelitis ◽  
Healthy Donors

Tetraspanins are a conserved family of proteins involved in a number of biological processes including, cell–cell interactions, fertility, cancer metastasis and immune responses. It has previously been shown that TSPAN32 knockout mice have normal hemopoiesis and B-cell responses, but hyperproliferative T cells. Here, we show that TSPAN32 is expressed at higher levels in the lymphoid lineage as compared to myeloid cells. In vitro activation of T helper cells via anti-CD3/CD28 is associated with a significant downregulation of TSPAN32. Interestingly, engagement of CD3 is sufficient to modulate TSPAN32 expression, and its effect is potentiated by costimulation with anti-CD28, but not anti-CTLA4, -ICOS nor -PD1. Accordingly, we measured the transcriptomic levels of TSPAN32 in polarized T cells under Th1 and Th2 conditions and TSPAN32 resulted significantly reduced as compared with unstimulated cells. On the other hand, in Treg cells, TSPAN32 underwent minor changes upon activation. The in vitro data were finally translated into the context of multiple sclerosis (MS). Encephalitogenic T cells from Myelin Oligodendrocyte Glycoprotein (MOG)-Induced Experimental Autoimmune Encephalomyelitis (EAE) mice showed significantly lower levels of TSPAN32 and increased levels of CD9, CD53, CD82 and CD151. Similarly, in vitro-activated circulating CD4 T cells from MS patients showed lower levels of TSPAN32 as compared with cells from healthy donors. Overall, these data suggest an immunoregulatory role for TSPAN32 in T helper immune response and may represent a target of future immunoregulatory therapies for T cell-mediated autoimmune diseases.

scholarly journals STAT5 promotes accessibility and is required for BATF-mediated plasticity at the Il9 locus

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Yongyao Fu ◽  
Jocelyn Wang ◽  
Gayathri Panangipalli ◽  
Benjamin J. Ulrich ◽  
Byunghee Koh ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cell Differentiation ◽  
Tumor Immunity ◽  
Th17 Cells ◽  
Allergic Airway Inflammation ◽  
T Helper Cell ◽  
T Helper ◽  
Th9 Cells ◽  
Specific Manner ◽  
Pioneer Factor

Abstract T helper cell differentiation requires lineage-defining transcription factors and factors that have shared expression among multiple subsets. BATF is required for development of multiple Th subsets but functions in a lineage-specific manner. BATF is required for IL-9 production in Th9 cells but in contrast to its function as a pioneer factor in Th17 cells, BATF is neither sufficient nor required for accessibility at the Il9 locus. Here we show that STAT5 is the earliest factor binding and remodeling the Il9 locus to allow BATF binding in both mouse and human Th9 cultures. The ability of STAT5 to mediate accessibility for BATF is observed in other Th lineages and allows acquisition of the IL-9-secreting phenotype. STAT5 and BATF convert Th17 cells into cells that mediate IL-9-dependent effects in allergic airway inflammation and anti-tumor immunity. Thus, BATF requires the STAT5 signal to mediate plasticity at the Il9 locus.

scholarly journals T Helper 17 Cells in Autoimmune Liver Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Masanori Abe ◽  
Yoichi Hiasa ◽  
Morikazu Onji
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Autoimmune Diseases ◽  
Th17 Cells ◽  
Transforming Growth Factor ◽  
Treg Cells ◽  
Reciprocal Relationship ◽  
Th2 Cells ◽  
T Helper ◽  
T Helper 17

Many autoimmune diseases are driven by self-reactive T helper (Th) cells. A new population of effector CD4+T cells characterized by the secretion of interleukin (IL)-17, referred to as Th17 cells, has been demonstrated to be phenotypically, functionally, and developmentally distinct from Th1 and Th2 cells. Because the liver is known to be an important source of transforming growth factor-βand IL-6, which are cytokines that are crucial for Th17 differentiation, it is very likely that Th17 cells contribute to liver inflammation and autoimmunity. In contrast, another distinct subset of T cells, regulatory T cells (Treg), downregulate immune responses and play an important role in maintaining self-tolerance. In addition, there is a reciprocal relationship between Th17 cells and Tregs, in development and effector functions, and the balance between Th17 and Treg cells can affect the outcome of immune responses, particularly in autoimmune diseases. In this review, we will focus on the latest investigative findings related to Th17 cells in autoimmune liver disease.

scholarly journals Thy1+IL-7+ lymphatic endothelial cells in iBALT provide a survival niche for memory T-helper cells in allergic airway inflammation

2016 ◽  
Vol 113 (20) ◽  
pp. E2842-E2851 ◽  
Author(s):  
Kenta Shinoda ◽  
Kiyoshi Hirahara ◽  
Tomohisa Iinuma ◽  
Tomomi Ichikawa ◽  
Akane S. Suzuki ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Airway Inflammation ◽  
Allergic Inflammation ◽  
Allergic Airway Inflammation ◽  
Th2 Cells ◽  
Lymphatic Endothelial Cells ◽  
T Helper ◽  
Th Cells ◽  
Memory Type ◽  
Lymphoid Structures

Memory CD4+ T helper (Th) cells are central to long-term protection against pathogens, but they can also be pathogenic and drive chronic inflammatory disorders. How these pathogenic memory Th cells are maintained, particularly at sites of local inflammation, remains unclear. We found that ectopic lymphoid-like structures called inducible bronchus-associated lymphoid tissue (iBALT) are formed during chronic allergic inflammation in the lung, and that memory-type pathogenic Th2 (Tpath2) cells capable of driving allergic inflammation are maintained within the iBALT structures. The maintenance of memory Th2 cells within iBALT is supported by Thy1+IL-7–producing lymphatic endothelial cells (LECs). The Thy1+IL-7–producing LECs express IL-33 and T-cell–attracting chemokines CCL21 and CCL19. Moreover, ectopic lymphoid structures consisting of memory CD4+ T cells and IL-7+IL-33+ LECs were found in nasal polyps of patients with eosinophilic chronic rhinosinusitis. Thus, Thy1+IL-7–producing LECs control chronic allergic airway inflammation by providing a survival niche for memory-type Tpath2 cells.

scholarly journals Guidance of super-enhancers in regulation of IL-9 induction and airway inflammation

2018 ◽  
Vol 215 (2) ◽  
pp. 559-574 ◽  
Author(s):  
Xiang Xiao ◽  
Yihui Fan ◽  
Junhui Li ◽  
Xiaolong Zhang ◽  
Xiaohua Lou ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Allergic Airway Inflammation ◽  
T Helper ◽  
Allergic Lung Inflammation ◽  
Th9 Cells ◽  
Cell Induction ◽  
Chromatin Acetylation ◽  
Th9 Cell

Th9 cells are prominently featured in allergic lung inflammation, but the mechanism that regulates IL-9 induction in T helper cells remains poorly defined. Here we demonstrate that formation of super-enhancers (SEs) is critical in robust induction of IL-9 and that assembly of the Il9 SEs in Th cells requires OX40-triggered chromatin acetylation. Mechanistically, we found that OX40 costimulation induces RelB expression, which recruits the histone acetyltransferase p300 to the Il9 locus to catalyze H3K27 acetylation. This allows binding of the SE factor Brd4 to organize assembly of the SE complex, which in turn drives robust IL-9 expression and Th9 cell induction. Thus, Th9 cells are strongly induced upon OX40 stimulation, and disruption of SEs abolished Th9 cell induction in vitro and inhibited Th9 cell–mediated allergic airway inflammation in vivo. Together, our data suggest that formation of SEs is essential in IL-9 expression and Th9 cell induction. These findings may have important clinical implications.

scholarly journals Metformin alleviates allergic airway inflammation and increases Treg cells in obese asthma

2021 ◽  
Vol 25 (4) ◽  
pp. 2279-2284
Author(s):  
Yimin Guo ◽  
Jianting Shi ◽  
Qiujie Wang ◽  
Luna Hong ◽  
Ming Chen ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Allergic Airway Inflammation ◽  
Treg Cells

scholarly journals Development of Autologous, Oligoclonal, Poorly Functioning T Lymphocytes in a Patient With Autosomal Recessive Severe Combined Immunodeficiency Caused by Defects of the Jak3 Tyrosine Kinase

Blood ◽  
1998 ◽  
Vol 91 (3) ◽  
pp. 949-955 ◽  
Author(s):  
Duilio Brugnoni ◽  
Luigi D. Notarangelo ◽  
Alessandra Sottini ◽  
Paolo Airò ◽  
Marta Pennacchio ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Tyrosine Kinase ◽  
Cd4 T Cells ◽  
Severe Combined Immunodeficiency ◽  
Combined Immunodeficiency ◽  
T Helper ◽  
T Helper 1 ◽  
In Vitro Susceptibility ◽  
And Function

Abstract Defects of the common gamma chain subunit of the cytokine receptors (γc) or of Jak3, a tyrosine kinase required for γc signal transduction, result in T−B+ severe combined immunodeficiency (SCID). However, atypical cases, characterized by progressive development of T lymphocytes, have been also reported. We describe a child with SCID caused by Jak3 gene defects, which strongly but not completely affect Jak3 protein expression and function, who developed a substantial number (>3,000/μL) of autologous CD3+CD4+ T cells. These cells showed a primed/activated phenotype (CD45R0+ Fas+HLA-DR+ CD62Llo), defective secretion of T-helper 1 and T-helper 2 cytokines, reduced proliferation to mitogens, and a high in vitro susceptibility to spontaneous (caused by downregulation of bcl-2 expression) as well as activation-induced cell death. A restricted T-cell receptor repertoire was observed, with oligoclonal expansion within each of the dominant segments. These features resemble those observed in γc-/y and in Jak3−/−mice, in which a population of activated, anergic T cells (predominantly CD4+) also develops with age. These results suggest that residual Jak3 expression and function or other Jak3-independent signals may also permit the generation of CD4+ T cells that undergo in vivo clonal expansion in humans; however, these mechanisms do not allow development of CD8+ T cells, nor do they fully restore the functional properties of CD4+ T lymphocytes.

Sign in / Sign up

Export Citation Format

Share Document