Expression of Th2-skewed pathology mediators in monocyte-derived type 2 of dendritic cells (DC2).
The information conveyed from dendritic cells (DCs) to naïve CD4(+) T cells has crucial influence on their differentiation toward effector T cells. In an effort to identify DC-derived molecules directly contributing to T cell differentiation, we searched for molecules distinctively expressed between two DC subtypes, which were differentiated from peripheral monocytes by cultivation with GM-CSF (for DC1) or IL-3 (for DC2) in the presence of IL-4 and had the ability to induce naïve T cells to differentiate into Th1 or Th2 cells, respectively. As the first step to address this issue, we subtracted DC1 transcripts from those of DC2 and compiled the gene profile dominantly expressed in DC2, whose products are known to reside in other than the nucleus. Intriguingly, many of them were molecules involved in Th2-skewed disease pathologies, such as FN1, ITGAE, GPNMB, PLAUR, FPRL2, LILRB4, SERPINE1, ALOX15, TBXAS1, NCF2, CCL3, IL1RN, SPARC, and STAB1, suggesting that DCs function not only as antigen presenting cells but also as producers of Th2 pathology specific milieus leading to disease deteriorations. We also found that expressions of CYP27A1, PPAP2B, RSAD2, and ABCC3 were up-regulated in DC2, implying their significant function in Th2-deviated states. The identification of differentially expressed genes between DC subtypes provides new insights into their functions and our comparative gene expression profile will be highly useful for the identification of DC-derived key molecules for T cell differentiation.
Hata
Mitsumi
M
The Fifth Frontier Project, Daiichi Pharmaceutical Co., Ltd., Tokyo 134-8630, Japan.
Takahara
Seiji
S
Tsuzaki
Hidetoshi
H
Ishii
Yoshiki
Y
Nakata
Koh
K
Akagawa
Kiyoko S
KS
Satoh
Kazuki
K
D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005353:Fibronectins / Q000235:genetics; D020869:Gene Expression Profiling; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D039001:Integrin alpha Chains / Q000235:genetics; D007371:Interferon-gamma / Q000378:metabolism; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000097802:CD83 Antigen
D015703:Antigens, CD; D051940:B7-2 Antigen; D053493:Cholestanetriol 26-Monooxygenase; D005353:Fibronectins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D007136:Immunoglobulins; D039001:Integrin alpha Chains; D007371:Interferon-gamma; D007377:Interleukin-3; D015847:Interleukin-4; D015848:Interleukin-5; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen; C091367:alpha E integrins; C506831:CYP27A1 protein, human