CD137 ligand signaling enhances myelopoiesis during infections

Area of Science:

• Immunology
• Hematology

Background:

• Conflicting data exist regarding the role of the CD137 receptor-ligand system in regulating myelopoiesis (the production of myeloid cells).
• CD137(-/-) mice exhibit increased myeloid cell numbers in bone marrow (BM), suggesting an inhibitory role, yet CD137 also promotes hematopoietic progenitor cell proliferation and myeloid differentiation.

Purpose of the Study:

• To investigate the context-dependent regulation of myelopoiesis by the CD137-CD137L system.
• To reconcile conflicting data by examining CD137's role during infection-induced inflammation.

Main Methods:

• Mice were infected with various pathogens (Influenza, Bordetella pertussis, Mycobacterium bovis, Escherichia coli) or treated with lipopolysaccharide (LPS).
• CD137 expression on BM cells, particularly CD4(+) T cells, was analyzed.
• Coculture experiments assessed the ability of CD137-expressing CD4(+) T cells to influence BM and hematopoietic progenitor cells.
• Myeloid cell proliferation and numbers in CD137(-/-) and wild-type mice during infection were compared.

Main Results:

• Infections and LPS treatment significantly increased CD137-expressing cells, especially CD4(+) T cells, in mouse BM.
• CD137-expressing CD4(+) T cells induced proliferation and myeloid differentiation of BM and hematopoietic progenitor cells in vitro.
• Mice lacking CD137 (CD137(-/-)) showed diminished infection-induced increases in myeloid cell proliferation and numbers in the BM.

Conclusions:

• CD137-CD137L interactions inhibit myelopoiesis under steady-state conditions.
• During infections, CD137-expressing CD4(+) T cells enhance myelopoiesis, promoting myeloid cell proliferation and differentiation.
• The CD137 system plays a dual role in myelopoiesis, dependent on the physiological context of inflammation or infection.