Allergen Exposure in Lymphopenic Fas-Deficient Mice Results in Persistent Eosinophilia Due to Defects in Resolution of Inflammation

Autor(es)

Ferreira, Caroline M. ^[1] ; Williams, Jesse W. ^{[2, 3]} ; Tong, Jiankun ^[2] ; Rayon, Crystal ^[1] ; Blaine, Kelly M. ^[1] ; Sperling, I, Anne

Afiliação do(s) autor(es)

^[1] I, Univ Chicago, Dept Med, Sect Pulm & Crit Care Med, 5841 S Maryland Ave, Chicago, IL 60637 - USA

^[2] Univ Chicago, Dept Pathol, 5841 S Maryland Ave, Chicago, IL 60637 - USA

^[3] I, Univ Chicago, Comm Mol Pathol & Mol Med, Chicago, IL 60637 - USA

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN IMMUNOLOGY; v. 9, OCT 30 2018.
• Citações Web of Science: 0

Resumo

Asthma is characterized by chronic airway type-2 inflammation and eosinophilia, yet the mechanisms involved in chronic, non-resolving inflammation remain poorly defined. Previously, our group has found that when Rag-deficient mice were reconstituted with Fas-deficient B6 LPR T cells and sensitized and challenged, the mice developed a prolonged type-2-mediated airway inflammation that continued for more than 6 weeks after the last antigen exposure. Surprisingly, no defect in resolution was found when intact B6 LPR mice or T cell specific Fas-conditional knockout mice were sensitized and challenged. We hypothesize that the homeostatic proliferation induced by adoptive transfer of T cells into Rag-deficient mice may be an important mechanism involved in the lack of resolution. To investigate the role of homeostatic proliferation, we induced lymphopenia in the T cell-specific Fas-conditional knockout mice by non-lethal irradiation and sensitized them when T cells began to repopulate. Interestingly, we found that defective Fas signaling on T cells plus antigen exposure during homeostatic proliferation was sufficient to induce prolonged eosinophilic airway inflammation. In conclusion, our data show that the combination of transient lymphopenia, abnormal Fas-signaling, and antigen exposure leads to the development of a prolonged airway eosinophilic inflammatory phase in our mouse model of experimental asthma. (AU)

• Processo FAPESP: 12/50410-8 - Efeito dos ácidos graxos de cadeia curta produzidos por bactérias probióticas na profilaxia e tratamento da inflamação alérgica das vias aéreas
• Beneficiário: Caroline Marcantonio Ferreira
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores