Adoptive transfer of bone marrow-derived dendritic cells (BMDCs) alleviates OVA-induced allergic airway inflammation in asthmatic mice

Kan Xu,Zhihui Min,Juan Song,Zhihong Chen,Ruolin Mao,Zhilong Jiang,Hong Ji,Nan Wu,Yuzhen Zeng,Chunfang Liu,Tao Zhu,Zheng Li

doi:10.1038/s41598-020-70467-3

Abstract

Airway dendritic cells (DCs) are recognized as important factors in the mechanisms of allergic inflammatory diseases. Suppressor of cytokine signaling 3 (SOCS3) is involved in regulating the functions of T cells and macrophages, but the roles of SOCS3-expressing DCs in the pathogeneses of allergic inflammatory diseases are still controversial. We compared the effects of adoptively transferred SOCS3−/− and SOCS3+/+ bone marrow-derived DCs (BMDCs) on airway inflammation in ovalbumin (OVA)-sensitized asthmatic mice. Adoptive transfer of mature DCs (lipopolysaccharide [LPS]-induced DCs, DClps) with or without SOCS3 gene expression significantly ameliorated allergic airway inflammation. SOCS3−/− DCs slightly attenuated BMDC-induced immunogenic tolerance. DClps migrated to OVA-sensitized lungs with higher efficiency than immature DCs (DCim). DClps with or without SOCS3 greatly improved lung pathology scores and alleviated airway inflammatory cell infiltration after adoptive transfer into mice; they also increased interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) production and inhibited signal transducer and activator of transcription (STAT) 4 and STAT6 signaling in the lungs after OVA sensitization. In conclusion, the BMDC adoptive transfer-induced immunogenic tolerance in OVA-sensitized mice might not be due to SOCS3 gene depletion. BMDC adoptive transfer may be developed into a new approach that alleviates asthma by modulating the balance between immune tolerance and inflammation.

Highlights

Airway dendritic cells (DCs) play crucial roles in initiating effective adaptive immune responses against invading pathogens and inducing immune tolerance toward innocuous inhaled antigens
Duan et al found that deletion of Suppressor of cytokine signaling 3 (SOCS3) in macrophages enhanced the expression of STAT1-stimulated genes in response to IL-6
Our previously published data revealed that SOCS3-deficient bone marrow-derived macrophages (BMDMs) expressed relatively high levels of TNF-α and that adoptive transfer of SOCS3-deficient BMDMs into WT mice enhanced the severity of acute lung injury (ALI)[10]

Summary

Introduction

Airway dendritic cells (DCs) play crucial roles in initiating effective adaptive immune responses against invading pathogens and inducing immune tolerance toward innocuous inhaled antigens. Emerging literature has demonstrated that different DC subsets and discrete functional states of DCs might be responsible for promoting tolerance to inhaled antigenic substances. T cell-specific deletion of SOCS3 impairs the T helper (Th) 2 response and increases Th1 responses[7]. Deletion of SOCS3 in hematopoietic cells results in severe inflammatory disease during adult life that is not rescued by IL-6 d eletion[8]. The roles of the SOCS3 gene in DC functional states and the cognate interaction of SOCS3 with T cells have been controversial. DCs with SOCS3 gene deletion in different functional states were adoptively transferred into ovalbumin (OVA)-sensitized mice, and lung pathological injury and airway inflammatory cell infiltration were evaluated.

Methods

Results

Conclusion