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Human Langerhans cells induce distinct IL-22-producing CD4+ T cells lacking IL-17 production.
Proc Natl Acad Sci U S A. 2009 Dec 22; 106(51):21795-800.PN

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.

Authors+Show Affiliations

Laboratory for Investigative Dermatology and Translational Immunomonitoring Resource Center, The Rockefeller University, New York, NY 10065, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19996179

Citation

Fujita, Hideki, et al. "Human Langerhans Cells Induce Distinct IL-22-producing CD4+ T Cells Lacking IL-17 Production." Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 51, 2009, pp. 21795-800.
Fujita H, Nograles KE, Kikuchi T, et al. Human Langerhans cells induce distinct IL-22-producing CD4+ T cells lacking IL-17 production. Proc Natl Acad Sci U S A. 2009;106(51):21795-800.
Fujita, H., Nograles, K. E., Kikuchi, T., Gonzalez, J., Carucci, J. A., & Krueger, J. G. (2009). Human Langerhans cells induce distinct IL-22-producing CD4+ T cells lacking IL-17 production. Proceedings of the National Academy of Sciences of the United States of America, 106(51), 21795-800. https://doi.org/10.1073/pnas.0911472106
Fujita H, et al. Human Langerhans Cells Induce Distinct IL-22-producing CD4+ T Cells Lacking IL-17 Production. Proc Natl Acad Sci U S A. 2009 Dec 22;106(51):21795-800. PubMed PMID: 19996179.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human Langerhans cells induce distinct IL-22-producing CD4+ T cells lacking IL-17 production. AU - Fujita,Hideki, AU - Nograles,Kristine E, AU - Kikuchi,Toyoko, AU - Gonzalez,Juana, AU - Carucci,John A, AU - Krueger,James G, Y1 - 2009/12/08/ PY - 2009/12/10/entrez PY - 2009/12/10/pubmed PY - 2010/2/19/medline SP - 21795 EP - 800 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc Natl Acad Sci U S A VL - 106 IS - 51 N2 - 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. SN - 1091-6490 UR - https://www.unboundmedicine.com/medline/citation/19996179/Human_Langerhans_cells_induce_distinct_IL_22_producing_CD4+_T_cells_lacking_IL_17_production_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=19996179 DB - PRIME DP - Unbound Medicine ER -