Follicular T Helper and Breg Cell Balance in Severe Allergic Asthma Before and After Omalizumab Therapy

Abstract

Background Severe allergic asthma (SAA) is based on type 2 (T2-high) immune responses to allergens promoting type 2 T helper (Th2) cell cytokine responses and production of IgE antibodies. Omalizumab was the first biological drug licensed for clinical use in the management of IgE-mediated SAA. Despite emerging evidence supporting the prominent role of follicular T cells (Tfh), Breg and Treg subsets, in the development and progression of SAA, no data are available on the impact of omalizumab therapy. Methods Ten SAA patients monitored at the Respiratory Diseases Unit of Siena University Hospital and ten healthy sex-and age-matched controls were enrolled in the study. Clinical and functional parameters were collected at baseline (T0) and after 6 months of therapy (T6). Cellular population analysis was determined through multicolour flow cytometry. Results SAA patients showed higher percentages of Th17.1, Tfh and Tfh2 while CD24 hi CD27 hi Breg cell, Treg and Tfr percentages were significantly lower than in controls. Higher percentages of Tfh2 in patients with nasal polyps than in those without and in controls were observed. At T6, significant decreases in Tfh and Tfh2 compared with T0 were observed. A slightly significant increase in Teffs was reported at T6 compared to T0. ΔIgE levels in serum were correlated with ΔCD19 + CD24 + CD27 + Breg cell percentages (r = − 0.86, p = 0.0022). Conclusions Our data explored the changes in Tfh cells, Tregs and Bregs in severe asthma. The restoration of immunological imbalance in SAA patients after omalizumab is certainly intriguing and represents a glimpse into the comprehension of immunological effects of treatment.L. Bergantini and M. d'Alessandro contributed equally to the study.

Crosstalk between ILC2s and Th2 CD4+ T Cells in Lung Disease

“…Fasting can inhibit the proliferation of Th2 cells in the lung and downregulate the level of Th2 cytokines [ 68 ]. The percentage of Th17.1, Tfh, and Tfh2 was higher in severe allergic asthma patients, while the percentage of Breg cells and Treg was significantly lower than in the control group [ 69 ]. This immune imbalance was restored after omalizumab treatment [ 69 ].…”

“…The percentage of Th17.1, Tfh, and Tfh2 was higher in severe allergic asthma patients, while the percentage of Breg cells and Treg was significantly lower than in the control group [ 69 ]. This immune imbalance was restored after omalizumab treatment [ 69 ]. Anti-F4/80 treatment of OVA-induced asthmatic mice inhibited alternately activated macrophages and also attenuated Th2 cell response in lung tissue [ 70 ].…”

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“…Although the imbalance of effector Th cell immune response and Treg cell immunosuppression in asthma has been broadly observed and characterized (85)(86)(87)(88), the underlying mechanism is still unclear. It is generally believed that effector Th cell immune response and Treg cell immunosuppression are regulated by different mechanisms, resulting in different effects.…”

NK and T Cell Immunological Signatures in Hospitalized Patients with COVID-19

“…Briefly, the peripheral blood samples were collected and processed within 8 h Ficoll density gradient separation was performed through Ficoll Histopaque®-1077 (Sigma-Aldrich, Burlington, MA, USA) as previously reported Live cell counts were performed in a Burker chamber. Aliquots of 3 × 10 6 cells were stored in liquid nitrogen in a standardised manner as previously reported [26][27][28][29][30]. All experiments were performed after thawing under the same conditions.…”

“…For multiparametric flow cytometry analysis, we used a standard staining protocol for extracellular markers [26]. Briefly, cells were washed with wash buffer (HBSS−/− with 2% FBS) and incubated with Ab mix for 30 min in the dark at RT.…”