IRF4 promotes cutaneous dendritic cell migration to lymph nodes during homeostasis and inflammation.
IRF4 promotes cutaneous dendritic cell migration to lymph nodes during homeostasis and inflammation.
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DOI：
10.4049/jimmunol.1102613
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发表时间：
2012-10-01
期刊：
影响因子：
--
通讯作者：
Kovats S
中科院分区：
文献类型：
--
作者：
Bajaña S;Roach K;Turner S;Paul J;Kovats S
在皮肤感染、自身免疫性疾病和疫苗接种过程中，驻留的树突状细胞（DC）从皮肤迁移到局部淋巴结（LN）触发T细胞介导的免疫应答。在这里，我们调查了是否发展和迁移的皮肤居民DC的干扰素调节因子4（IRF 4），一个转录因子，是需要的CD 11b+脾DC的发展。我们发现，未经处理的IRF 4 −/−小鼠的皮肤含有正常数量的表皮朗格汉斯细胞（eLC）和增加数量的CD 11b+和CD 103+真皮DC群体，表明组织DC发育和皮肤驻留不会被IRF 4缺陷破坏。相反，迁移性eLC和CD 11b+真皮DC的数量在IRF 4 −/−小鼠的皮肤LN中显著减少，表明在稳态期间从真皮的组成性迁移存在缺陷。在诱导皮肤炎症后，IRF 4 −/−小鼠中的CD 11b+真皮DC不表达趋化因子受体CCR 7，并且不能迁移到皮肤LN，而eLC的迁移仅轻度受损。因此，尽管IRF 4对它们的发育至关重要，但IRF 4对CCR 7介导的CD 11b+真皮DC的迁移至关重要，真皮DC是小鼠和人皮肤中的主要群体，在正常和致病性皮肤免疫中起着至关重要的作用。
Migration of resident dendritic cells (DC) from the skin to local lymph nodes (LN) triggers T cell-mediated immune responses during cutaneous infection, autoimmune disease and vaccination. Here we investigated whether the development and migration of skin resident DC were regulated by interferon regulatory factor 4 (IRF4), a transcription factor that is required for the development of CD11b+ splenic DC. We found that the skin of naïve IRF4−/− mice contained normal numbers of epidermal Langerhans cells (eLC) and increased numbers of CD11b+ and CD103+ dermal DC populations, indicating that tissue DC development and skin residency is not disrupted by IRF4 deficiency. In contrast, numbers of migratory eLC and CD11b+ dermal DC were significantly reduced in the cutaneous LN of IRF4−/− mice, suggesting a defect in constitutive migration from the dermis during homeostasis. Upon induction of skin inflammation, CD11b+ dermal DC in IRF4−/− mice did not express the chemokine receptor CCR7, and failed to migrate to cutaneous LN, while the migration of eLC was only mildly impaired. Thus, while dispensable for their development, IRF4 is crucial for the CCR7-mediated migration of CD11b+ dermal DC, a predominant population in murine and human skin that plays a vital role in normal and pathogenic cutaneous immunity.
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影响因子：
9.1
作者：
Johnson-Huang, Leanne M.;McNutt, N. Scott;Krueger, James G.;Lowes, Michelle A.
通讯作者：
Lowes, Michelle A.
DOI：
10.4049/jimmunol.1001802
发表时间：
2010-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bobr A;Olvera-Gomez I;Igyarto BZ;Haley KM;Hogquist KA;Kaplan DH
通讯作者：
Kaplan DH
影响因子：
4.4
作者：
Shklovskaya, Elena;Roediger, Ben;Fazekas de St Groth, Barbara
通讯作者：
Fazekas de St Groth, Barbara
影响因子：
15.3
作者：
Moodycliffe, AM;Shreedhar, V;Flores-Romo, L
通讯作者：
Flores-Romo, L
影响因子：
15.3
作者：
King, Irah L.;Kroenke, Mark A.;Segal, Benjamin M.
通讯作者：
Segal, Benjamin M.