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The origin and development of nonlymphoid tissue CD103+ DCs.

Florent Ginhoux1, Kang Liu, Julie Helft

  • 1Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.

The Journal of Experimental Medicine
|December 17, 2009
PubMed
Summary

CD103(+) dendritic cells (DCs) in nonlymphoid tissues develop from the same precursors as lymphoid organ CD8(+) DCs. Their differentiation is regulated by specific transcription factors, revealing shared developmental pathways.

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Area of Science:

  • Immunology
  • Cell Biology
  • Developmental Biology

Background:

  • CD103(+) dendritic cells (DCs) in nonlymphoid tissues are crucial for antigen cross-presentation.
  • The developmental mechanisms regulating these specialized DCs remain largely uncharacterized.

Purpose of the Study:

  • To investigate the developmental origins and regulatory mechanisms of CD103(+) DCs in nonlymphoid tissues.
  • To compare the differentiation pathways of nonlymphoid tissue CD103(+) DCs with lymphoid organ CD8(+) DCs.

Main Methods:

  • Flow cytometry to identify and separate distinct DC populations based on CD103, CD11b, and MHCII expression.
  • Analysis of gene expression and developmental dependencies, including fms-like tyrosine kinase 3 (Flt3) ligand, inhibitor of DNA protein 2 (Id2), IFN regulatory protein 8 (IRF8), and MCSF-R.

Main Results:

  • Two CD11c(+)MHCII(+) DC populations, distinguished by CD103 and CD11b, exist in nonlymphoid tissues (except lamina propria).
  • Nonlymphoid tissue CD103(+) DCs share developmental requirements (Flt3 ligand, Id2, IRF8) with lymphoid organ CD8(+) DCs, indicating a common precursor.
  • Lamina propria CD103(+) DCs exhibit distinct development, expressing CD11b and being Id2/IRF8 independent.
  • The CD103(-)CD11b(+) DC population is heterogeneous and relies on Flt3 and MCSF-R.

Conclusions:

  • Nonlymphoid tissue CD103(+) DCs and lymphoid organ CD8(+) DCs originate from the same precursor and share a related differentiation program.
  • Distinct regulatory pathways govern the development of different DC subsets within nonlymphoid tissues.