Quantitative and functional impairment of pulmonary CD4+CD25hi regulatory T cells in pediatric asthma

Hartl, Dominik; Koller, Barbara; Mehlhorn, Alexander T.; Reinhardt, D.; Nicolaï, Thomas; Schendel, Dolores J.; Griese, Matthias; Krauss‐Etschmann, Susanne

doi:10.1016/j.jaci.2007.02.023

Cited by 362 publications

(337 citation statements)

References 38 publications

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“…Many recent studies have also examined the role of Foxp3 and CD4 + CD25 + Treg cells in allergic asthma and atopic patients (21). Peripheral blood mononuclear cells from allergic rhinitis and asthma patients have significantly fewer Foxp3 + lymphocytes and decreased Foxp3 mRNA expression (22,23). Tregs from atopic patients have less suppressive activity compared with the ones from nonatopic groups (24), suggesting that Foxp3 and Treg have an important role in regulating hypersensitive immune responses in human patients.…”

mentioning

confidence: 99%

Cell-permeable Foxp3 protein alleviates autoimmune disease associated with inflammatory bowel disease and allergic airway inflammation

Choi

Shin

Sohn

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Foxp3 is a key transcription factor for differentiation and function of regulatory T (Treg) cells that is critical for maintaining immunological self-tolerance. Therefore, increasing Treg function by Foxp3 transduction to regulate an inflammatory immune response is an important goal for the treatment of autoimmune and allergic diseases. Here we have generated a cell-permeable Foxp3 protein by fusion with the unique human HHph-1-PTD (protein transduction domain), examined its regulatory function in T cells, and characterized its therapeutic effect in autoimmune and allergic disease models. HHph-1-Foxp3 was rapidly and effectively transduced into cells within 30 min and conferred suppressor function to CD4 + CD25 − T cells as well as directly inhibiting T-cell activation and proliferation. Systemic delivery of HHph-1 Foxp3 remarkably inhibited the autoimmune symptoms of scurfy mice and the development of colitis induced by scurfy or wild-type CD4 T cells. Moreover, intranasal delivery of HHph-1-Foxp3 strongly suppressed ovalbumin-induced allergic airway inflammation. These results demonstrate the clinical potential of the cell-permeable recombinant HHph-1-Foxp3 protein in autoimmune and hypersensitive allergic diseases.

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mentioning

confidence: 99%

Cell-permeable Foxp3 protein alleviates autoimmune disease associated with inflammatory bowel disease and allergic airway inflammation

Choi

Shin

Sohn

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…The levels of Foxp3 mRNA in BAL from children with asthma are lower than in healthy controls, positively correlate with FEV1 and, after 4 weeks of treatment with inhaled corticosteroids, significantly increase [3]. Furthermore, in severe asthmatics, the Foxp3 protein expression in PBMC correlates with the FEV1 values and with the symptom score [29].…”

Section: Discussionmentioning

confidence: 95%

“…T-lymphocytes play a crucial role in the development of airway inflammation. Particularly, Tregs exert an important role in the control of T-cell-mediated inflammation in asthma [3,4]. Two major subsets of Tregs are identified: CD25highly þ Foxp3þ Tregs and IL-10-producing Tregs.…”

Section: Introductionmentioning

confidence: 99%

Budesonide increases TLR4 and TLR2 expression in Treg lymphocytes of allergic asthmatics

Pace

Sano

Ferraro

et al. 2015

Pulmonary Pharmacology & Therapeutics

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“…Numerous reports have discussed the contribution of naturally occurring Tregs to the immune control of CD4 + T lymphocytes in pulmonary disorders (19,42). The absence of nTregs has been found to provoke the random development of autoimmune diseases in athymic mice (46) in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…Studies have shown that the nTregs of pediatric asthma patients are fewer in number and are more likely to be dysfunctional than those of healthy subjects and corticosteroid-treated asthma patients (19). Similarly, decreased expression of Foxp3 in regulatory T cells (Tregs) has been observed in the small airways of patients with COPD (20).…”

mentioning

confidence: 99%

CD4+CD25+Foxp3+ Regulatory T Cells Are Dispensable for Controlling CD8+ T Cell-Mediated Lung Inflammation

Tosiek

Gruber

Bader

et al. 2011

The Journal of Immunology

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Every person harbors a population of potentially self-reactive lymphocytes controlled by tightly balanced tolerance mechanisms. Failures in this balance evoke immune activation and autoimmunity. In this study, we investigated the contribution of self-reactive CD8+ T lymphocytes to chronic pulmonary inflammation and a possible role for naturally occurring CD4+CD25+Foxp3+ regulatory T cells (nTregs) in counterbalancing this process. Using a transgenic murine model for autoimmune-mediated lung disease, we demonstrated that despite pulmonary inflammation, lung-specific CD8+ T cells can reside quiescently in close proximity to self-antigen. Whereas self-reactive CD8+ T cells in the inflamed lung and lung-draining lymph nodes downregulated the expression of effector molecules, those located in the spleen appeared to be partly Ag-experienced and displayed a memory-like phenotype. Because ex vivo-reisolated self-reactive CD8+ T cells were very well capable of responding to the Ag in vitro, we investigated a possible contribution of nTregs to the immune control over autoaggressive CD8+ T cells in the lung. Notably, CD8+ T cell tolerance established in the lung depends only partially on the function of nTregs, because self-reactive CD8+ T cells underwent only biased activation and did not acquire effector function after nTreg depletion. However, although transient ablation of nTregs did not expand the population of self-reactive CD8+ T cells or exacerbate the disease, it provoked rapid accumulation of activated CD103+CD62Llo Tregs in bronchial lymph nodes, a finding suggesting an adaptive phenotypic switch in the nTreg population that acts in concert with other yet-undefined mechanisms to prevent the detrimental activation of self-reactive CD8+ T cells.

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Quantitative and functional impairment of pulmonary CD4+CD25hi regulatory T cells in pediatric asthma

Cited by 362 publications

References 38 publications

Cell-permeable Foxp3 protein alleviates autoimmune disease associated with inflammatory bowel disease and allergic airway inflammation

Cell-permeable Foxp3 protein alleviates autoimmune disease associated with inflammatory bowel disease and allergic airway inflammation

Budesonide increases TLR4 and TLR2 expression in Treg lymphocytes of allergic asthmatics

CD4+CD25+Foxp3+ Regulatory T Cells Are Dispensable for Controlling CD8+ T Cell-Mediated Lung Inflammation

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