CD73 is expressed by inflammatory Th17 cells in experimental autoimmune encephalomyelitis but does not limit differentiation or pathogenesis.

Gerard Hernandez-Mir,Mandy J Mcgeachy,Thomas Forsthuber

doi:10.1371/journal.pone.0173655

Abstract

CD73 works together with CD39 to convert extracellular ATP to immunoregulatory adenosine, thus inhibiting inflammation. TGFβ-mediated CD73 expression on ‘regulatory’ Th17 cells limits their ability to eradicate tumors, similar to the immunosuppressive mechanism described for CD73 on Tregs. However, CD73 is also expressed on Th17 cells thought to be inflammatory in Crohn’s disease. CD73 has previously been reported to contribute to inflammation in the central nervous system (CNS). In experimental autoimmune encephalomyelitis (EAE), we found that inflammatory cytokine-producing Th17 cells showed increased CD73 expression as disease progressed. We therefore hypothesized that CD73 could be important for limiting the expansion or pathogenic function of Th17 cells in autoimmune inflammation of the CNS. Surprisingly, EAE development was not enhanced or inhibited by CD73 deficiency; there was correspondingly no difference in induction of Th17-associated cytokines IL-17, IFNγ or GM-CSF or recruitment of either inflammatory or regulatory cells to the central nervous system. We confirmed that CD73 was similarly not required for differentiation of Th17 cells in vitro. These data show that while CD73 expression is regulated during EAE, this enzyme is not absolutely required to either promote or limit Th17 cell expansion or EAE severity.

Highlights

Th17 cells produce cytokines including IL-17, GM-CSF and IFNγ that orchestrate immune and tissue inflammatory responses resulting in recruitment and activation of myeloid cells, as well as production of antimicrobial peptides and matrix metalloproteinases
CD73 expression is increased on TGFβ-stimulated Th17 cells and regulatory T cells in vitro, while remaining low on Th0 and Th1 cells (Fig 1A), confirming previous reports
We demonstrated that a large proportion of Th17 cells expressed CD73 during EAE induction, and this increased as EAE progressed

Summary

Introduction

Th17 cells produce cytokines including IL-17, GM-CSF and IFNγ that orchestrate immune and tissue inflammatory responses resulting in recruitment and activation of myeloid cells, as well as production of antimicrobial peptides and matrix metalloproteinases. These responses are beneficial in controlling extracellular bacteria and fungal pathogens such as Staphylococcus aureus and Candida albicans, as well as promoting wound healing following resolution of the infection[1, 2]. These non-pathogenic Th17 cells have been termed ‘regulatory’ Th17 cells due to their capacity to suppress inflammation through production of IL-10, there are multiple mechanisms determining their non-pathogenic phenotype[9, 10]

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Conclusion