TY - JOUR
T1 - Reciprocal cytokine-mediated cellular interactions in mouse epidermis
T2 - promotion of γδ t-cell growth by il-7 and tnfα and inhibition of keratinocyte growth by γifn
AU - Matsue, Hiroyuki
AU - Bergstresser, Paul R.
AU - Takashima, Akira
PY - 1993/10
Y1 - 1993/10
N2 - A unique subset of γδ T cells, termed dendritic epidermal T cells (DETC), resides in symbiosis with keratinocytes in mouse epidermis. We have shown previously that interleukin 7 (IL-7) which is produced by keratinocytes, promotes growth and prevents apoptosis in DETC. To extend this observation, we examined 12 cytokines, each of which is expressed by epidermal cells at mRNA and/or protein levels, for their capacities to modulate the growth of DETC. Cytokines examined included IL-1α, IL-2, IL-3, IL-4, IL-6, IL-7, IL-8, IL-10, tumor necrosis factor-α (TNFγ), interferon-γ-(IFNγ), granulocyte/macrophage-colony stimulating factor (GM-CSF), and macrophage inflammatory protein-1α (MIP-lα). When tested individually, IL-2 and IL-7 promoted maximal growth of the long-term cultured DETC line 7-17. When tested in combinations, synergistic growth-promoting effects were seen with IL-2 and IL-4 or IL-7, and with IL-7 and IL-4 or TNFα. Dose-response experiments demonstrated that TNFα, which is produced by keratinocytes, enhances IL-7-induced DETC proliferation, but inhibits IL-2-induced proliferation. The mouse keratinocyte-derived cell line Pam 212 was used to test these cytokines for their capacities to regulate keratinocyte growth. Only γIFN, which is produced by DETC, inhibited proliferation in a dose-dependent fashion. These results illustrate three reciprocal pathways by which epidermal cytokines regulate the growth of epidermal cells: 1) a paracrine mechanism by which keratinocyte-derived cytokines (e.g., IL-7 and TNFα) promote the growth of DETC, 2) an autocrine mechanism by which DETC-derived cytokines (e.g., IL-2 and IL-4) support their own growth, and 3) a reciprocal pathway in which a cytokine produced by resident epidermal leukocytes (e.g., γIFN) modulates the growth of keratinocytes.
AB - A unique subset of γδ T cells, termed dendritic epidermal T cells (DETC), resides in symbiosis with keratinocytes in mouse epidermis. We have shown previously that interleukin 7 (IL-7) which is produced by keratinocytes, promotes growth and prevents apoptosis in DETC. To extend this observation, we examined 12 cytokines, each of which is expressed by epidermal cells at mRNA and/or protein levels, for their capacities to modulate the growth of DETC. Cytokines examined included IL-1α, IL-2, IL-3, IL-4, IL-6, IL-7, IL-8, IL-10, tumor necrosis factor-α (TNFγ), interferon-γ-(IFNγ), granulocyte/macrophage-colony stimulating factor (GM-CSF), and macrophage inflammatory protein-1α (MIP-lα). When tested individually, IL-2 and IL-7 promoted maximal growth of the long-term cultured DETC line 7-17. When tested in combinations, synergistic growth-promoting effects were seen with IL-2 and IL-4 or IL-7, and with IL-7 and IL-4 or TNFα. Dose-response experiments demonstrated that TNFα, which is produced by keratinocytes, enhances IL-7-induced DETC proliferation, but inhibits IL-2-induced proliferation. The mouse keratinocyte-derived cell line Pam 212 was used to test these cytokines for their capacities to regulate keratinocyte growth. Only γIFN, which is produced by DETC, inhibited proliferation in a dose-dependent fashion. These results illustrate three reciprocal pathways by which epidermal cytokines regulate the growth of epidermal cells: 1) a paracrine mechanism by which keratinocyte-derived cytokines (e.g., IL-7 and TNFα) promote the growth of DETC, 2) an autocrine mechanism by which DETC-derived cytokines (e.g., IL-2 and IL-4) support their own growth, and 3) a reciprocal pathway in which a cytokine produced by resident epidermal leukocytes (e.g., γIFN) modulates the growth of keratinocytes.
KW - epidermal γδ T cell/keratinocyte/growth/cytokine
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U2 - 10.1111/1523-1747.ep12365938
DO - 10.1111/1523-1747.ep12365938
M3 - Article
C2 - 8409521
AN - SCOPUS:0027424517
SN - 0022-202X
VL - 101
SP - 543
EP - 548
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 4
ER -