Assessment of Allergen-Responsive Regulatory T Cells in Experimental Asthma Induced in Different Mouse Strains.

Autor:	Azevedo CT; Laboratório de Inflamação, Instituto Oswaldo Cruz, FIOCRUZ, Brazil.; Laboratório de Estudos em Imunologia, Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro (UFRJ), Av. Carlos Chagas Filho 373, Bloco A 2º Andar sala 07, Cidade Universitária, Ilha do Fundão, CEP. 21941-902 Rio de Janeiro, Brazil., Cotias AC; Laboratório de Inflamação, Instituto Oswaldo Cruz, FIOCRUZ, Brazil., Arantes ACS; Laboratório de Inflamação, Instituto Oswaldo Cruz, FIOCRUZ, Brazil., Ferreira TPT; Laboratório de Inflamação, Instituto Oswaldo Cruz, FIOCRUZ, Brazil., Martins MA; Laboratório de Inflamação, Instituto Oswaldo Cruz, FIOCRUZ, Brazil., Olsen PC; Laboratório de Estudos em Imunologia, Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro (UFRJ), Av. Carlos Chagas Filho 373, Bloco A 2º Andar sala 07, Cidade Universitária, Ilha do Fundão, CEP. 21941-902 Rio de Janeiro, Brazil.
Jazyk:	angličtina
Zdroj:	Mediators of inflammation [Mediators Inflamm] 2021 Dec 10; Vol. 2021, pp. 7584483. Date of Electronic Publication: 2021 Dec 10 (Print Publication: 2021).
DOI:	10.1155/2021/7584483
Abstrakt:	Background: Regulatory T cells (Tregs) are important in regulating responses to innocuous antigens, such as allergens, by controlling the Th2 response, a mechanism that appears to be compromised in atopic asthmatic individuals. Different isogenic mouse strains also have distinct immunological responses and susceptibility to the experimental protocols used to develop lung allergic inflammation. In this work, we investigated the differences in the frequency of Treg cell subtypes among A/J, BALB/c, and C57BL/6, under normal conditions and following induction of allergic asthma with ovalbumin (OVA). Methods: Subcutaneous sensitization followed by 4 consecutive intranasal OVA challenges induced asthma characteristic changes such as airway hyperreactivity, inflammation, and production of Th2 cytokines (IL-4, IL-13, IL-5, and IL-33) in the lungs of only A/J and BALB/c but not C57BL/6 strain and evaluated by invasive whole-body plethysmography, flow cytometry, and ELISA, respectively. Results: A/J strain naturally showed a higher frequency of CD4 + IL-10 + T cells in the lungs of naïve mice compared to the other strains, accompanied by higher frequencies of CD4 + IL-4 + T cells. C57BL/6 mice did not develop lung inflammation and presented higher frequency of CD4 + CD25 + Foxp3 + Treg cells in the bronchoalveolar lavage fluid (BALF) after the allergen challenge. In in vitro settings, allergen-specific stimulation of mediastinal LN (mLN) cells from OVA-challenged animals induced higher frequency of CD4 + IL-10 + Treg cells from A/J strain and CD4 + CD25 + Foxp3 + from C57BL/6. Conclusions: The observed differences in the frequencies of Treg cell subtypes associated with the susceptibility of the animals to experimental asthma suggest that CD4 + CD25 + Foxp3 + and IL-10-producing CD4 + Treg cells may play different roles in asthma control. Similar to asthmatic individuals, the lack of an efficient regulatory response and susceptibility to the development of experimental asthma in A/J mice further suggests that this strain could be preferably chosen in experimental models of allergic asthma. Competing Interests: There are no conflicts of interest for all named author. (Copyright © 2021 C. T. Azevedo et al.)
Databáze:	MEDLINE
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