CD103⁺ CD11b^- salivary gland dendritic cells have antigen cross-presenting capacity

Dendritic cells (DCs) in lymphoid and non-lymphoid tissues are professional antigen-presenting cells that are essential for effective immunity and tolerance. However, the presence and characteristics of DCs in steady-state salivary glands (SGs) currently remain unknown. We herein identified CD64^- CD11c⁺ classical DCs (cDCs) as well as CD64⁺ macrophages among CD45⁺ MHC class II⁺ antigen-presenting cells in steady-state murine SGs. SG cDCs were divided into CD103⁺ CD11b^- and CD103^- CD11b⁺ cDCs. CD103⁺ CD11b^- cDCs expressed XCR1, CLEC9A, and interferon regulatory factor 8, whereas CD103^- CD11b⁺ cDCs strongly expressed CD172a. Both cDC subsets in SGs markedly expanded in response to the Flt3 ligand (Flt3L), were replenished by bone marrow-derived precursors, and differentiated from common DC precursors, but not monocytes. Furthermore, ovalbumin-pulsed SG CD103⁺ CD11b^- cDCs induced the proliferation of naïve ovalbumin-specific CD8⁺ T cells and production of interferon-γ from proliferating T cells. SG CD103⁺ CD11b^- cDCs expanded by Flt3L in vivo exhibited the same properties. These results indicate that bona fide cDCs reside in steady-state murine SGs and cDCs with the CD103⁺ CD11b^- phenotype possess antigen cross-presenting capacity. Moreover, Flt3L enhances protective immunity by expanding cDCs. Taken together, SG cDCs might play an important role in maintaining immune homeostasis in the tissues.