IRF4 Transcription Factor-Dependent CD11b⁺ Dendritic Cells in Human and Mouse Control Mucosal IL-17 Cytokine Responses

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• 作者：Andreas Schlitzer¹ ; ⁹ ; Naomi McGovern² ; ⁹ ; Pearline Teo¹ ; Teresa Zelante¹ ; Koji Atarashi³ ; Donovan Low¹ ; Adrian W.S. Ho¹ ; Peter See¹ ; Amanda Shin¹ ; Pavandip Singh Wasan¹ ; Guillaume Hoeffel¹ ; Benoit Malleret¹ ; Alexander Heiseke⁴ ; Samantha Chew¹ ; Laura Jardine² ; Harriet A. Purvis² ; Catharien M.U. Hilkens² ; John Tam⁵ ; ⁶ ; Michael Poidinger¹ ; E. Richard Stanley⁷ ; Anne B. Krug⁴ ; Laurent Renia¹ ; Baalasubramanian Sivasankar⁸ ; Lai Guan Ng¹ ; Matthew Collin² ; Paola Ricciardi-Castagnoli¹ ; Kenya Honda³ ; Muzlifah Haniffa² ; Florent Ginhoux¹ ; ^{florent_ginhoux@immunol.a-star.edu.sg}
• 刊名：Immunity
• 出版年：2013
• 出版时间：23 May, 2013
• 年：2013
• 卷：38
• 期：5
• 页码：970-983
• 全文大小：3403 K

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Summary

Mouse and human dendritic cells (DCs) are composed of functionally specialized subsets, but precise interspecies correlation is currently incomplete. Here, we showed that murine lung and gut lamina propria CD11b⁺ DC populations were comprised of two subsets: FLT3- and IRF4-dependent CD24⁺CD64^? DCs and contaminating CSF-1R-dependent CD24^?CD64⁺ macrophages. Functionally, loss of CD24⁺CD11b⁺ DCs abrogated CD4⁺ T?cell-mediated interleukin-17 (IL-17) production in steady state and after Aspergillus fumigatus challenge. Human CD1c⁺ DCs, the equivalent of murine CD24⁺CD11b⁺ DCs, also expressed IRF4, secreted IL-23, and promoted T helper 17 cell responses. Our data revealed heterogeneity in the mouse CD11b⁺ DC compartment and identifed mucosal tissues IRF4-expressing DCs specialized in?instructing IL-17 responses in both mouse and human. The demonstration of mouse and human DC subsets specialized in driving IL-17 responses highlights the conservation of key immune functions across species and will facilitate the translation of mouse in?vivo findings to advance DC-based clinical therapies.