Abstract
Epidermal Langerhans cells (LC) are considered direct yet immature precursors of dendritic cells (DC) in the draining lymph nodes. Although the development of LC into potent immunostimulatory DC occurs in vitro and has been studied in detail, little is known about their profile of cytokine gene expression. By using reverse transcriptase polymerase chain reaction analysis to screen 16 cytokines followed by Northern blotting for selected analysis, we determined the cytokine gene expression profile of murine LC at different time points in culture when T cell stimulatory activity is increasing profoundly. LC regularly expressed macrophage inflammatory proteins, MIP-1 alpha and MIP-2, and interleukin 1 beta (IL-1 beta). Both MIPs were downregulated upon culture and maturation into DC, whereas IL-1 beta was strongly upregulated in culture. MIP-1 alpha and IL-1 beta mRNA were found only in LC, but not in other epidermal cells. Apart from trace amounts of IL- 6 in cultured LC, several macrophage and T cell products were not detected. The cytokine expression profile of LC thus appears distinct from typical macrophages. The exact role of the cytokine genes we found transcribed in LC remains to be determined.
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- Chiu C. P., Moulds C., Coffman R. L., Rennick D., Lee F. Multiple biological activities are expressed by a mouse interleukin 6 cDNA clone isolated from bone marrow stromal cells. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7099–7103. doi: 10.1073/pnas.85.19.7099. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dallman M. J., Larsen C. P., Morris P. J. Cytokine gene transcription in vascularised organ grafts: analysis using semiquantitative polymerase chain reaction. J Exp Med. 1991 Aug 1;174(2):493–496. doi: 10.1084/jem.174.2.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Enk A. H., Katz S. I. Early molecular events in the induction phase of contact sensitivity. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1398–1402. doi: 10.1073/pnas.89.4.1398. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fahey T. J., 3rd, Tracey K. J., Tekamp-Olson P., Cousens L. S., Jones W. G., Shires G. T., Cerami A., Sherry B. Macrophage inflammatory protein 1 modulates macrophage function. J Immunol. 1992 May 1;148(9):2764–2769. [PubMed] [Google Scholar]
- Graham G. J., Wright E. G., Hewick R., Wolpe S. D., Wilkie N. M., Donaldson D., Lorimore S., Pragnell I. B. Identification and characterization of an inhibitor of haemopoietic stem cell proliferation. Nature. 1990 Mar 29;344(6265):442–444. doi: 10.1038/344442a0. [DOI] [PubMed] [Google Scholar]
- Gray P. W., Glaister D., Chen E., Goeddel D. V., Pennica D. Two interleukin 1 genes in the mouse: cloning and expression of the cDNA for murine interleukin 1 beta. J Immunol. 1986 Dec 1;137(11):3644–3648. [PubMed] [Google Scholar]
- Koch F., Heufler C., Kämpgen E., Schneeweiss D., Böck G., Schuler G. Tumor necrosis factor alpha maintains the viability of murine epidermal Langerhans cells in culture, but in contrast to granulocyte/macrophage colony-stimulating factor, without inducing their functional maturation. J Exp Med. 1990 Jan 1;171(1):159–171. doi: 10.1084/jem.171.1.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Koide S., Steinman R. M. Induction of murine interleukin 1: stimuli and responsive primary cells. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3802–3806. doi: 10.1073/pnas.84.11.3802. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Larrick J. W., Morhenn V., Chiang Y. L., Shi T. Activated Langerhans cells release tumor necrosis factor. J Leukoc Biol. 1989 May;45(5):429–433. doi: 10.1002/jlb.45.5.429. [DOI] [PubMed] [Google Scholar]
- Larsen C. P., Steinman R. M., Witmer-Pack M., Hankins D. F., Morris P. J., Austyn J. M. Migration and maturation of Langerhans cells in skin transplants and explants. J Exp Med. 1990 Nov 1;172(5):1483–1493. doi: 10.1084/jem.172.5.1483. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Romani N., Koide S., Crowley M., Witmer-Pack M., Livingstone A. M., Fathman C. G., Inaba K., Steinman R. M. Presentation of exogenous protein antigens by dendritic cells to T cell clones. Intact protein is presented best by immature, epidermal Langerhans cells. J Exp Med. 1989 Mar 1;169(3):1169–1178. doi: 10.1084/jem.169.3.1169. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Romani N., Kämpgen E., Koch F., Heufler C., Schuler G. Dendritic cell production of cytokines and responses to cytokines. Int Rev Immunol. 1990;6(2-3):151–161. doi: 10.3109/08830189009056626. [DOI] [PubMed] [Google Scholar]
- Romani N., Schuler G. The immunologic properties of epidermal Langerhans cells as a part of the dendritic cell system. Springer Semin Immunopathol. 1992;13(3-4):265–279. doi: 10.1007/BF00200527. [DOI] [PubMed] [Google Scholar]
- Sauder D. N., Dinarello C. A., Morhenn V. B. Langerhans cell production of interleukin-1. J Invest Dermatol. 1984 Jun;82(6):605–607. doi: 10.1111/1523-1747.ep12261439. [DOI] [PubMed] [Google Scholar]
- Schuler G., Steinman R. M. Murine epidermal Langerhans cells mature into potent immunostimulatory dendritic cells in vitro. J Exp Med. 1985 Mar 1;161(3):526–546. doi: 10.1084/jem.161.3.526. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Steinman R. M. The dendritic cell system and its role in immunogenicity. Annu Rev Immunol. 1991;9:271–296. doi: 10.1146/annurev.iy.09.040191.001415. [DOI] [PubMed] [Google Scholar]
- Streilein J. W., Grammer S. F. In vitro evidence that Langerhans cells can adopt two functionally distinct forms capable of antigen presentation to T lymphocytes. J Immunol. 1989 Dec 15;143(12):3925–3933. [PubMed] [Google Scholar]
- Tekamp-Olson P., Gallegos C., Bauer D., McClain J., Sherry B., Fabre M., van Deventer S., Cerami A. Cloning and characterization of cDNAs for murine macrophage inflammatory protein 2 and its human homologues. J Exp Med. 1990 Sep 1;172(3):911–919. doi: 10.1084/jem.172.3.911. [DOI] [PMC free article] [PubMed] [Google Scholar]