An increase of CD83+ dendritic cells ex vivo correlates with increased regulatory T cells in patients with active eosinophilic granulomatosis and polyangiitis

BMC Immunology

Kazuo Akiyama⁴  Hiroyuki Mitomi³  Miyako Ishiyama¹  Takahiro Tsuburai²  Chiyako Oshikata²  Hiroshi Saito⁴  Naomi Tsurikisawa² 

[1] Laboratory Medicine, Kanagawa Rehabilitation Hospital, 516 Nanasawa Atsugi, Kanagawa 243-0121, Japan;Departments of Allergy and Respirology, 18-1 Sakuradai, Minami-ku Sagamihara 252-0392, Kanagawa, Japan;Department of Surgical and Molecular Pathology, Dokkyo Medical University, 880 Kitakobayashi, Shimotsuga-gun, Mibu-machi 321-0293, Tochigi, Japan;Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, 18-1 Sakuradai, Minami-ku Sagamihara 252-0392, Kanagawa, Japan

关键词: Regulatory T cell;    EGPA;    Eosinophilic granulomatosis with polyangiitis;    Dendritic cell;    Churg–Strauss syndrome;   

Others  :  1077707
DOI  :  10.1186/s12865-014-0032-5

 received in 2014-03-10, accepted in 2014-08-08,  发布年份 2014

【 摘 要 】

Background

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare disease characterized by the presence of allergic granulomatosis and necrotizing vasculitis with eosinophilic infiltration. The etiology of EGPA is unknown. Dendritic cells (DCs) are not only critical for the induction of primary immune responses; they may also be important for the induction of immunological tolerance and the regulation of the type of T-cell-mediated immune response. To investigate whether DC maturation is associated with EGPA disease status, we examined the relationship between the maturation of DCs and the differentiation of regulatory T (T_reg) cells in EGPA patients. We exposed the CD14⁺ blood monocytes of 19 patients with EGPA in remission or relapse to stimulation with GM-CSF and IL-4 for 6 d and lipopolysaccharide for 24 h to obtain mature CD83⁺ DCs and immature CD206⁺ DCs. Using immunohistochemistry, we examined four patients for the presence of CD83⁺ and CD206⁺ DCs in the lung at the onset of EGPA.

Results

The percentage of CD83⁺ cells among DCs differentiated from CD14⁺ monocytes was lower for EGPA patients in relapse than in remission. The percentage of CD83⁺ DCs was inversely correlated with the percentage of CD206⁺ DCs and was significantly correlated with the numbers of naturally occurring CD4⁺ regulatory T_reg (nT_reg; FOXP3⁺CD4⁺) cells and inducible Treg (iTreg; CD4⁺CD25⁺ T cells producing IL-10 or TGF-β) cells but not the number of eosinophils. The percentage of CD206⁺ DCs was significantly inversely correlated with the percentages of nT_reg and iTreg cells but not the number of eosinophils. Immunohistochemistry revealed both CD206⁺ DCs and CD83⁺ DCs in alveoli and interstitial spaces at the onset of EGPA.

Conclusion

The maturation of DCs from monocytes was related to disease activity in patients with EGPA. Increased CD83⁺ DCs in EGPA patients may induce the differentiation of iT_reg and nT_reg cells, thereby suppressing inflammation and disease activity.

【 授权许可】

   
2014 Tsurikisawa et al.; licensee BioMed Central Ltd.

【 图 表 】

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