Abstract:
:Colony-stimulating factor 1 (CSF1) and interleukin 34 (IL34) signal via the CSF1 receptor to regulate macrophage differentiation. Studies in IL34- or CSF1-deficient mice have revealed that IL34 function is limited to the central nervous system and skin during development. However, the roles of IL34 and CSF1 at homeostasis or in the context of inflammatory diseases or cancer in wild-type mice have not been clarified in vivo. By neutralizing CSF1 and/or IL34 in adult mice, we identified that they play important roles in macrophage differentiation, specifically in steady-state microglia, Langerhans cells, and kidney macrophages. In several inflammatory models, neutralization of both CSF1 and IL34 contributed to maximal disease protection. However, in a myeloid cell-rich tumor model, CSF1 but not IL34 was required for tumor-associated macrophage accumulation and immune homeostasis. Analysis of human inflammatory conditions reveals IL34 upregulation that may account for the protection requirement of IL34 blockade. Furthermore, evaluation of IL34 and CSF1 blockade treatment during Listeria infection reveals no substantial safety concerns. Thus, IL34 and CSF1 play non-redundant roles in macrophage differentiation, and therapeutic intervention targeting IL34 and/or CSF1 may provide an effective treatment in macrophage-driven immune-pathologies.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Lin W,Xu D,Austin CD,Caplazi P,Senger K,Sun Y,Jeet S,Young J,Delarosa D,Suto E,Huang Z,Zhang J,Yan D,Corzo C,Barck K,Rajan S,Looney C,Gandham V,Lesch J,Liang WC,Mai E,Ngu H,Ratti N,Chen Y,Misner D,Lin Tdoi
10.3389/fimmu.2019.02019subject
Has Abstractpub_date
2019-09-04 00:00:00pages
2019issn
1664-3224journal_volume
10pub_type
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