Th9 Cells and Parasitic Inflammation: Use of Nippostrongylus and Schistosoma Models

Author(s):  
Miguel Enrique Serrano Pinto ◽  
Paula Licona-Limón
Keyword(s):  
2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1197.2-1198
Author(s):  
N. Mohannad ◽  
M. Moaaz ◽  
R. Mohamed Shehata

Background:SLE is an autoimmune disease (AID) of unknown origin. Several factors can contribute to immune dysfunction in SLE.Interleukin 9 (IL9) is a newly emerging T cell-derived factor preferentially expressed by CD4+T cells: T helper 9 (Th9)IL9 targets different cell lineages, and can contribute to the development of allergic & AIDsWhether abnormal expression and secretion of IL9 are present in SLE patients (pts) still unidentified. It is also unclear whether IL9 exerts main proinflammatory or anti-inflammatory activities in SLE. T1DM is characterized by inflammation of the pancreatic islets of Langerhans. Insulitis progresses over time and β cells become destroyed then clinical DM is established. T1DM is regarded as a T cell-driven AIDObjectives:Evaluation of the expression of CD4+ IL9+ T cells & the level of IL9 in SLE pts compared to both healthy subjects & pts with another AID: T1DM.Also, to evaluate the correlation of these expressions with clinical features, laboratory parameters and SLE activityMethods:The study included: Group I 25 SLE pts fulfilling SLICC classification criteria divided into 2 subgroups (gps) according to SLE disease activity index (SLEDAI) IA: 20 pts with mild to moderate activity (<12) IB:5 pts with severe activity (>12) recruited from rheumatology clinic or internal medicine ward (Rheumatology unit), Main University Hospital, Alexandria. Group II 15 healthy individuals as a first control gp. Group III 15 pts with T1DM fulfilling the American Diabetes Association criteria as a second control gp. All pts were subjected to history taking, clinical examination,laboratory investigations: CBC,LFT,KFT,ESR,CRP,ANA,Anti-dsDNA,Th9 cell expression detection by flowcytometry and serum IL9 by ELISAResults:There was no statistical difference between all gps as regards age & sex but a significant increased ESR in SLE compared to controls & T1DM p< 0.001 p=0.001Th9 expression was highly increased in SLE pts, range 0.13-4.54% & mean ±SD=1.50 ± 1.47% than both control gps. In healthy controls Th9 ranged between 0.0-1.29% with mean 0.37 ±0.52%, while in T1DM pts ranged between 0.03 to 2.13% with mean of 0.67 ± 0.59%. A high significant difference was found between SLE pts and controls p=0.001, an insignificant rise was seen in SLE pts compared to T1DM pts p=0.157. A high significant increase in Th9 was found in severe SLE: mean of 3.74 ±1.15% than in pts with mild to moderate SLE: mean 0.94±0.88% p=<0.001IL9 level was highly increased in SLE pts: mean of 42.83± 23.98 pg/ml than both control gps. In healthy controls the mean was 8.54±13.27, while in T1DM with mean of 29.17±16.09 pg/ml. A high significant difference was found between SLE pts and normal controls p<0.001 but an insignificant rise with T1DM p=0.294. A high significant increase in IL9 in pts with severe ds compared to mild to moderate pts p<0.001.A significant direct correlation between Th9 & IL9 and SLEDAI/105 A significant direct correlation between damage index and Th9 p=0.040 but not IL9 p=0.053In SLE no significant relation between Th9 or IL9 & clinical manifestations or disease duration. A direct correlations between Th9 & ESR p=0.046 and CRP p=0.025,a significant correlation between IL9 and CRP p=0.033, no correlations between Th9&IL9 level and anti-dsDNA p=0.593& 0.4 Significant direct correlation between Th9 and IL9 in T1DM pts, still no correlation with glycemic profile. IL9 levels were significantly increased in SLE with elevated CRP p=0.033 & the % of Th9 cells were increased with elevated ESR and CRP p=0.025, 0.046Conclusion:In SLE pts; IL9 level and Th9 cells expression were significantly elevated compared to healthy controls. IL9 levels and the percentages of Th9 directly correlated with the SLE disease activity. IL9 levels also were significantly increased in T1DM pts compared to controls,but they were less expressed than in SLE. This suggests an important role of IL9 in the pathogenesis AIDs as SLEReferences:[1]Tahernia L et al. Cytokines in SLE: their role in pathogenesis of disease and possible therapeutic opportunities. Rheum Res 2017Disclosure of Interests:None declared


2021 ◽  
pp. 101477
Author(s):  
Isis Benoit-Lizon ◽  
Lionel Apetoh

2016 ◽  
Vol 39 (1) ◽  
pp. 89-95 ◽  
Author(s):  
Benno Weigmann ◽  
Markus F. Neurath

2021 ◽  
Author(s):  
Stephanie Musiol ◽  
Francesca Alessandrini ◽  
Constanze A. Jakwerth ◽  
Adam M. Chaker ◽  
Evelyn Schneider ◽  
...  

TGF-β1 is known to have a pro-inflammatory impact by inducing Th9 cells, while it also induces anti-inflammatory Treg cells (Tregs). In the context of allergic airway inflammation (AAI) its dual role can be of critical importance in influencing the outcome of the disease. Here we demonstrate that TGF-β acts in AAI by driving effector T cells into Th9 cells, while Tregs differentiate independently. Induction of experimental AAI and airway hyperreactivity in a mouse model with inducible genetic ablation of the TGFβ-receptor 2 (TGFBR2) on CD4+T cells significantly reduced the disease phenotype. Further, it blocked the induction of Th9 cell frequencies, but increased Treg cells. To translate these findings into a human clinically relevant context, Th9 and Treg cells were quantified both locally in induced sputum and systemically in blood of allergic rhinitis and asthma patients with or without allergen-specific immunotherapy (AIT). Natural allergen exposure induced local and systemic Th2, Th9 cell and reduced Tregs, while therapeutic allergen exposure by AIT suppressed Th2 and Th9 cell frequencies along with TGF-β and IL-9 secretion. Altogether, these findings support that neutralization of TGF-β represents a viable therapeutic option in allergy and asthma, not posing the risk of immune dysregulation by impacting Tregs.


Author(s):  
Benjamin J. Ulrich ◽  
Matthew M. Hufford ◽  
Mark H. Kaplan
Keyword(s):  

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Ibrahim M. Khan, BS BA ◽  
Andrew S. Nelson, PhD ◽  
Mark H. Kaplan, PhD

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.


Animals ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 2137
Author(s):  
Kalibixiati Aimulajiang ◽  
Zhaohai Wen ◽  
Xiaowei Tian ◽  
Shakeel Ahmed Lakho ◽  
Yang Zhang ◽  
...  

Ephrin domain containing protein (EPH), a significant excreted and secreted product (ESPs) of Haemonchus contortus, has been identified to have antigenic functions. Over the past years, a new subset of CD4 + T named as T helper 9 cells that secrete interleukin-9 (IL-9) as a signature cytokine is associated with tumor immunity and allergy. Nonetheless, the understanding of immunomodulatory roles of EPH on goat Th9 and other immune cells remains limited. Herein, EPH from H. contortus (HcEPH) was cloned and expressed in pET-28a. Immunofluorescence assay (IFA) was carried-out to localize rHcEPH within H. contortus adult worms and to bind with goat peripheral blood mononuclear cells (PBMCs). Besides, the impact of rHcEPH on signature cytokine IL-9 expression in goat PBMCs was evaluated. Flow cytometry was employed to examine Th9 cells production and cell apoptosis. The results revealed success in the expression and localization of rHcEPH in surface of adult H. contortus gut sections. According to IFA analysis, the rHcEPH protein was capable to react precisely with anti-H. contortus antibodies. Further functional analysis showed that correlation between rHcEPH and host PBMCs significantly enhanced Th9 cell differentiation, IL-9 expression, cell apoptosis efficiency, and cell migration, whereas cell proliferation was suppressed significantly depending on the concentration. Our observations indicated that rHcEPH protein is linked to modulate the host immune cells and could enhance protective immunity by inducing Th9 responses.


Sign in / Sign up

Export Citation Format

Share Document