Receptor-type Protein-tyrosine Phosphatase ζ Is a Functional Receptor for Interleukin-34

CSF-1 Receptor Signaling in Myeloid Cells

“…Through their different spatiotemporal expression, the two ligands play complementary roles in regulating the development, maintenance, and activity of specific macrophage populations, Langerhans cells, neuronal progenitors (Wei et al 2010;Greter et al 2012;Nandi et al 2012;Wang et al 2012), as well as osteoclasts (Dai et al 2002) and Paneth cells (Huynh et al 2009) and the regulation of cells of the female reproductive tract (Wei et al 2010). Because all of the CSF-1 deficiency phenotypes are also shared with CSF-1R-deficient mice (Dai et al 2002), the CSF-1R appears to be the only receptor for CSF-1, whereas IL-34 has recently been shown to act via an additional receptor, receptortype protein tyrosine phosphatase-z (PTP-z) (Nandi et al 2013). …”

“…Thus caution should be taken in extrapolating results to different developmental stages, or types of macrophages. The existence of a new CSF-1R ligand, IL-34, that also interacts with PTP-z, which is coexpressed with the CSF-1R in several cell types, including HSC (Sarrazin et al 2009;Himburg et al 2012) and neural progenitors (von Holst et al 2006;Nandi et al 2013), may provide additional mechanisms for fine-tuning CSF-1R signaling in development, immunity, and disease. The discovery that Epstein -Barr virus encodes BamHI-A rightward frame-1 (BARF1), a secreted hexameric protein that binds the CSF-1 dimer interface with picomolar affinity and conformationally renders the cytokine unable to interact with the CSF-1R (Strockbine et al 1998;Elegheert et al 2012;Shim et al 2012), explains how Epstein -Barr virus eludes the immune response and offers a starting point for therapeutic targeting of both CSF-1 and BARF1.…”

Cytokines in the pathogenesis of rheumatoid arthritis: new players and therapeutic targets

“…The signal is transduced via cytoplasmic myeloid differentiation primary response protein 88 (MyD88) and IL-1R associated kinase 4 (IRAK4), ending up in the activation of transcriptions factors like NF-kB or MAPK [7]. IL-33 (IL-1F11) was identified in high ↑ vs HD, OA and PsA [70][71][72][73] ↑ in RA-ILD [71] ↑ in erosive RA [71] Lower baseline levels predict good response to anti-TNF-α agents [74,75] Detectable levels at baseline predict response to RTX [77] Detectable levels at baseline predict atherosclerotic plaque progression [76] na ↑ vs OA [26] = vs OA [72] Lower baseline levels predict good response to anti-TNF-α agents [74,75] IL-36 IL-36 is upregulated in CIA, CAIA and AIA [122,123] IL-36 blockade does not affect arthritis [122,123] ↑ vs HD [133] n a ↑ vs OA [126] IL-37 Systemic and intra-articular administration of recombinant IL-37 inhibits the development of synovitis in CIA and AIA [146,147] ↑ vs HD [133] ↑ vs HD and OA [147][148][149][150] ↑ in FR + and anti-CCP + patients vs seronegative [150] ↑ in active vs inactive RA [149] ↑ in erosive RA [150] ↑ [150] ↑ [147] IL-38 IL-38 KO mice display more severe AIA [131] IL-38 overexpression attenuates CIA and STIA [132] = vs HD and OA [131] ↑ vs HD [133] na ↑ vs OA [131] Other IL-32 IL-32 administration worsens CIA …”

Cytokine regulation of stem cells

“…IL-34 expression is generally high in brain tissues, and along with its receptor, it appears to be crucial for the development of microglial cells and their yolk sac precursors [37,38]. Interestingly, a new receptor of IL-34 namely receptor-type protein-tyrosine phosphatase has been discovered that expresses on neural progenitors, glial cells, and glioblastomas [39]. LIF promote differentiation of ES cells into neuronal cells, but inhibits the differentiation of ES cells to both mesodermal and extraembryonic endodermal lineages [40].…”