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Updated: Jun 17, 2026
Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes
Published on: September 26, 2013
Human Langerhans cells induce distinct IL-22-producing CD4+ T cells lacking IL-17 production
Hideki Fujita1, Kristine E Nograles, Toyoko Kikuchi
1Laboratory for Investigative Dermatology and Translational Immunomonitoring Resource Center, The Rockefeller University, New York, NY 10065, USA.
Insights
Cutaneous dendritic cells (DCs), particularly Langerhans cells (LCs), can induce unique IL-22-producing T cells, potentially Th22 cells, which may play a role in skin inflammation.
Area of Science:
- Immunology
- Dermatology
- Cell Biology
Background:
- Interleukin-22 (IL-22) is a cytokine crucial for epithelial cell function, implicated in skin inflammation and diseases like psoriasis.
- While initially linked to Th17 cells, IL-22 can be produced by T cells independently of IL-17.
- Unique IL-22-producing T cells exist in normal and inflamed skin, suggesting specialized roles.
Purpose of the Study:
- To investigate the capacity of cutaneous resident dendritic cells (DCs) to differentiate IL-22-producing T cells.
- To compare the inductive potential of Langerhans cells (LCs) versus dermal DCs (dDCs) in generating IL-22 producers.
- To characterize the cytokine profile of T cells induced by cutaneous DCs.
Main Methods:
- Isolation of LCs and dDCs from human epidermis and dermis using Fluorescence-Activated Cell Sorting (FACS).
- Mixed leukocyte reactions (MLRs) involving isolated DCs and T cells (peripheral blood or naive CD4+ T cells).
- Analysis of T cell cytokine production (IL-22, IL-17, IFN-gamma, IL-4) via flow cytometry and other assays.
Main Results:
- Both LCs and dDCs effectively induced IL-22-producing CD4+ and CD8+ T cells.
- LCs demonstrated a stronger capacity to induce IL-22-producing cells compared to dDCs.
- In vitro-generated LC-type DCs were more efficient than monocyte-derived DCs; induced IL-22 production correlated more with IFN-gamma than IL-17, and importantly, the majority of induced cells produced only IL-22, suggesting a 'Th22' phenotype.
Conclusions:
- Cutaneous DCs, especially LCs, are potent inducers of IL-22-producing T cells.
- These DCs preferentially generate T cells producing IL-22 alone (Th22 cells), distinct from Th17 cells.
- Cutaneous DCs may orchestrate the infiltration of specific Th22 cells into the skin, influencing inflammatory processes.
Abstract:
IL-22 is a cytokine that acts mainly on epithelial cells. In the skin, it mediates keratinocyte proliferation and epidermal hyperplasia and is thought to play a central role in inflammatory diseases with marked epidermal acanthosis, such as psoriasis. Although IL-22 was initially considered a Th17 cytokine, increasing evidence suggests that T helper cells can produce IL-22 even without IL-17 expression. In addition, we have shown the existence of this unique IL-22-producing T cell in normal skin and in the skin of psoriasis and atopic dermatitis patients. In the present study, we investigated the ability of cutaneous resident dendritic cells (DCs) to differentiate IL-22-producing cells. Using FACS, we isolated Langerhans cells (LCs; HLA-DR(+)CD207(+) cells) and dermal DCs (HLA-DR(hi)CD11c(+)BDCA-1(+) cells) from normal human epidermis and dermis, respectively. Both LCs and dermal DCs significantly induced IL-22-producing CD4(+) and CD8(+) T cells from peripheral blood T cells and naive CD4(+) T cells in mixed leukocyte reactions. LCs were more powerful in the induction of IL-22-producing cells than dermal DCs. Moreover, in vitro-generated LC-type DCs induced IL-22-producing cells more efficiently than monocyte-derived DCs. The induced IL-22 production was more correlated with IFN-gamma than IL-17. Surprisingly, the majority of IL-22-producing cells induced by LCs and dermal DCs lacked the expression of IL-17, IFN-gamma, and IL-4. Thus, LCs and dermal DCs preferentially induced helper T cells to produce only IL-22, possibly "Th22" cells. Our data indicate that cutaneous DCs, especially LCs, may control the generation of distinct IL-22 producing Th22 cells infiltrating into the skin.
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