Dendritic cells (DCs) are essential components of the immune system and contribute to immune responses by activating or tolerizing T cells. DCs comprise a heterogeneous mixture of subsets that are located throughout the body and possess distinct and specialized functions. Although numerous defined precursors from the bone marrow and spleen have been identified, emerging data in the field suggests many alternative routes of DC differentiation from precursors with multilineage potential. Here, we discuss how the combinatorial expression of transcription factors can promote one DC lineage over another as well as the integration of cytokine signaling in this process. 1. Introduction Dendritic cells (DCs) are professional antigen-presenting cells that bridge the gap between the innate and adaptive immune systems by acting as sentinels throughout the body to capture, process, and present antigen to T cells. Their ability to distinguish between self and nonself molecules allows them to deliver tolerizing or activating signals to T cells accordingly. Scientific exploration of DCs has become increasingly complex with the recognition that DCs exist as a heterogenous mixture of populations. Named for their cellular size and morphology [1], DCs all share the ability to activate na？ve T cells but exhibit unique functions within each subset. These DC populations have primarily been defined by their combinatorial cell surface marker expression, but they also differ in their developmental origins, transcriptional regulation, patterns of migration or residence, and anatomical and microenvironmental localization. DCs can be broadly classified as two major subsets: the inflammatory or infection-derived DCs, which develop from monocytes in response to stimulation, and the steady-state DCs, which are present at all times. The DCs present under steady state conditions include CD8+ and CD8？ conventional DCs (cDCs), plasmacytoid DCs (pDCs), and migratory CD103+ CD11b？ DCs, CD103？ CD11b+ DCs, and Langerhans cells (LCs) (Table 1). The CD8？ cDCs can be further classified as CD4+ or CD4？ DCs, which both express high levels of CD11b [2]. However, the majority of gene perturbation analyses that have examined CD8+ cDCs, CD8？ cDC, and pDCs as well as global gene analysis have shown mostly congruent gene expression between the CD4+ and CD4？ subsets [3]; thus, we will classify CD4+ and CD4？ DCs as CD8？ DCs for simplicity. Table 1: Surface molecule expression of steady state dendritic cell subsets. Phenotype of lymphoid-resident CD8 + cDC, CD8 ？ cDC, pDC, nonlymphoid tissue-resident
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