CX3CR1+ c-kit+ bone marrow cells give rise to CD103+ and CD103- dendritic cells with distinct functional properties

Maria-Luisa del Rio1, Jose-Ignacio Rodriguez-Barbosa, Jasmin Bölter

  • 1Institute of Immunology, Hannover Medical School, Hannover, Germany.

Insights

Bone marrow progenitor cells, specifically lineage-negative CX3CR1-positive c-kit-positive (GFP+c-kit+) cells, can differentiate into CD103-positive dendritic cells (DCs). These findings reveal a key source for replenishing CD103+ DCs in various organs.

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Dendritic cells (DCs) are a heterogeneous immune cell population crucial for immune responses.
  • CD103-positive (CD103+) DCs are a key subset involved in inducing tissue-specific homing of T cells, particularly at mucosal sites.
  • The progenitors responsible for replenishing the CD103+ DC subset remain largely unknown.

Purpose of the Study:

  • To identify and characterize bone marrow progenitors capable of differentiating into CD103+ DCs.
  • To investigate the distinct functional properties of CD103-negative (CD103-) and CD103+ DCs derived from identified progenitors.
  • To determine the contribution of these progenitors to CD103+ DC populations in vivo, especially during allergic inflammation.

Main Methods:

  • Isolation and in vitro/in vivo differentiation of lineage-negative CX3CR1-positive c-kit-positive (GFP+c-kit+) bone marrow cells.
  • Phenotypic analysis using flow cytometry to identify CD11c and CD103 expression.
  • Gene expression profiling and functional assays (phagocytosis, cytokine secretion, T cell proliferation).
  • Adoptive transfer experiments in irradiated mice with allergic lung inflammation.

Main Results:

  • GFP+c-kit+ bone marrow cells differentiated into both CD11c+CD103- and CD11c+CD103+ DCs in vitro and in vivo.
  • Generated CD103- DCs showed higher phagocytosis and secreted pro-inflammatory cytokines upon LPS stimulation.
  • Generated CD103+ DCs expressed high levels of costimulatory molecules and induced T cell proliferation.
  • Donor-derived CD103+ DCs were detected in the lungs and draining lymph nodes of recipient mice following adoptive transfer.

Conclusions:

  • Lineage-negative CX3CR1-positive c-kit-positive (GFP+c-kit+) bone marrow cells are progenitors for CD103+ DCs.
  • Distinct functional properties exist between CD103- and CD103+ DCs derived from these progenitors.
  • These progenitors contribute to the replenishment of CD103+ DCs in both lymphoid and non-lymphoid organs, including during inflammatory conditions.