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

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

Immunity

10.1016/j.immuni.2013.04.011

http://www.cell.com/immunity/retrieve/pii/S1074761313002057

Benoit Malleret, Pavandip Singh Wasan, Guillaume Hoeffel, Amanda Shin, Andreas Schlitzer, Naomi McGovern, Pearline Teo, Teresa Zelante, Koji Atarashi, Donovan Low, Adrian W.S. Ho, Peter See, Alexander Heiseke, Samantha Chew, Laura Jardine, Harriet A. Purvis, Catharien M.U. Hilkens, John Tam, Michael Poidinger, E. Richard Stanley, Anne B. Krug, Laurent Renia, Baalasubramanian Sivasankar, Lai Guan Ng, Matthew Collin, Paola Ricciardi-Castagnoli, Kenya Honda, Muzlifah Haniffa, Florent Ginhoux

23 May 2013

IRF4 Transcription Factor-Dependent CD11b+ Dendritic Cells in Human and Mouse Control Mucosal IL-17 Cytokine Responses Andreas Schlitzer, Naomi McGovern, Pearline Teo, Teresa Zelante, Koji Atarashi, Donovan Low, Adrian W.S. Ho, Peter See, Amanda Shin, Pavandip Singh Wasan, Guillaume Hoeffel, Benoit Malleret, Alexander Heiseke, Samantha Chew, Laura Jardine, Harriet A. Purvis, Catharien M.U. Hilkens, John Tam, Michael Poidinger, E. Richard Stanley, Anne B. Krug, Laurent Renia, Baalasubramanian Sivasankar, Lai Guan Ng, Matthew Collin, Paola Ricciardi-Castagnoli, Kenya Honda, Muzlifah Haniffa, Florent Ginhoux Immunity - 23 May 2013 (Vol. 38, Issue 5, pp. 970-983)

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.

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https://oar.a-star.edu.sg/communities-collections/articles/11607

1074-7613

Singapore Immunology Network