Transcription factor KLF10 constrains IL-17-committed Vγ4+ γδ T cells

γδ T cells, known to be an important source of innate IL-17 in mice, provide critical contributions to host immune responses. Development and function of γδ T cells are directed by networks of diverse transcription factors (TFs). Here, we examine the role of the zinc finger TFs, Kruppel-like factor 10 (KLF10), in the regulation of IL-17-committed CD27- γδ T (γδ27--17) cells. We found selective augmentation of Vγ4+ γδ27- cells with higher IL-17 production in KLF10-deficient mice. Surprisingly, KLF10-deficient CD127hi Vγ4+ γδ27--17 cells expressed higher levels of CD5 than their wild-type counterparts, with hyper-responsiveness to cytokine, but not T-cell receptor, stimuli. Thymic maturation of Vγ4+ γδ27- cells was enhanced in newborn mice deficient in KLF10. Finally, a mixed bone marrow chimera study indicates that intrinsic KLF10 signaling is requisite to limit Vγ4+ γδ27--17 cells. Collectively, these findings demonstrate that KLF10 regulates thymic development of Vγ4+ γδ27- cells and their peripheral homeostasis at steady state. © 2018 Kim, Gu, Kim, Ko, Kye, Kim, Cho, Lee, Song, Chu, Park, Han and Yu

Osteogenesis of Adipose-Derived and Bone Marrow Stem Cells with Polycaprolactone/Tricalcium Phosphate and Three-Dimensional Printing Technology in a Dog Model of Maxillary Bone Defects

Bone graft material should possess sufficient porosity and permeability to allow integration with native tissue and vascular invasion, and must satisfy oxygen and nutrient transport demands. In this study, we have examined the use of three-dimensional (3D)-printed polycaprolactone/tricalcium phosphate (PCL/TCP) composite material in bone grafting, to estimate the scope of its potential application in bone surgery. Adipose-derived stem cells (ADSCs) and bone marrow stem cells (BMSCs) are known to enhance osteointegration. We hypothesized that a patient-specific 3D-printed solid scaffold could help preserve seeded ADSCs and BMSCs and enhance osteointegration. Diffuse osteogenic tissue formation was observed by micro-computed tomography with both stem cell types, and the ADSC group displayed similar osteogenesis compared to the BMSC group. In histological assessment, the scaffold pores showed abundant ossification in both groups. Reverse transcription polymerase chain reaction (RT-PCR) showed that the BMSC group had higher expression of genes associated with ossification, and this was confirmed by Western blot analysis. The ADSC- and BMSC-seeded 3D-printed PCL/TCP scaffolds displayed promising enhancement of osteogenesis in a dog model of maxillary bone defects

Transcription Factor KLF10 Constrains IL-17-Committed Vγ4+ γδ T Cells

γδ T cells, known to be an important source of innate IL-17 in mice, provide critical contributions to host immune responses. Development and function of γδ T cells are directed by networks of diverse transcription factors (TFs). Here, we examine the role of the zinc finger TFs, Kruppel-like factor 10 (KLF10), in the regulation of IL-17-committed CD27− γδ T (γδ27−-17) cells. We found selective augmentation of Vγ4+ γδ27− cells with higher IL-17 production in KLF10-deficient mice. Surprisingly, KLF10-deficient CD127hi Vγ4+ γδ27−-17 cells expressed higher levels of CD5 than their wild-type counterparts, with hyper-responsiveness to cytokine, but not T-cell receptor, stimuli. Thymic maturation of Vγ4+ γδ27− cells was enhanced in newborn mice deficient in KLF10. Finally, a mixed bone marrow chimera study indicates that intrinsic KLF10 signaling is requisite to limit Vγ4+ γδ27−-17 cells. Collectively, these findings demonstrate that KLF10 regulates thymic development of Vγ4+ γδ27− cells and their peripheral homeostasis at steady state

Data_Sheet_6.PDF

<p>γδ T cells, known to be an important source of innate IL-17 in mice, provide critical contributions to host immune responses. Development and function of γδ T cells are directed by networks of diverse transcription factors (TFs). Here, we examine the role of the zinc finger TFs, Kruppel-like factor 10 (KLF10), in the regulation of IL-17-committed CD27⁻ γδ T (γδ²⁷⁻-17) cells. We found selective augmentation of Vγ4⁺ γδ²⁷⁻ cells with higher IL-17 production in KLF10-deficient mice. Surprisingly, KLF10-deficient CD127^hi Vγ4⁺ γδ²⁷⁻-17 cells expressed higher levels of CD5 than their wild-type counterparts, with hyper-responsiveness to cytokine, but not T-cell receptor, stimuli. Thymic maturation of Vγ4⁺ γδ²⁷⁻ cells was enhanced in newborn mice deficient in KLF10. Finally, a mixed bone marrow chimera study indicates that intrinsic KLF10 signaling is requisite to limit Vγ4⁺ γδ²⁷⁻-17 cells. Collectively, these findings demonstrate that KLF10 regulates thymic development of Vγ4⁺ γδ²⁷⁻ cells and their peripheral homeostasis at steady state.</p

Data_Sheet_3.PDF

<p>γδ T cells, known to be an important source of innate IL-17 in mice, provide critical contributions to host immune responses. Development and function of γδ T cells are directed by networks of diverse transcription factors (TFs). Here, we examine the role of the zinc finger TFs, Kruppel-like factor 10 (KLF10), in the regulation of IL-17-committed CD27⁻ γδ T (γδ²⁷⁻-17) cells. We found selective augmentation of Vγ4⁺ γδ²⁷⁻ cells with higher IL-17 production in KLF10-deficient mice. Surprisingly, KLF10-deficient CD127^hi Vγ4⁺ γδ²⁷⁻-17 cells expressed higher levels of CD5 than their wild-type counterparts, with hyper-responsiveness to cytokine, but not T-cell receptor, stimuli. Thymic maturation of Vγ4⁺ γδ²⁷⁻ cells was enhanced in newborn mice deficient in KLF10. Finally, a mixed bone marrow chimera study indicates that intrinsic KLF10 signaling is requisite to limit Vγ4⁺ γδ²⁷⁻-17 cells. Collectively, these findings demonstrate that KLF10 regulates thymic development of Vγ4⁺ γδ²⁷⁻ cells and their peripheral homeostasis at steady state.</p

Data_Sheet_1.PDF

<p>γδ T cells, known to be an important source of innate IL-17 in mice, provide critical contributions to host immune responses. Development and function of γδ T cells are directed by networks of diverse transcription factors (TFs). Here, we examine the role of the zinc finger TFs, Kruppel-like factor 10 (KLF10), in the regulation of IL-17-committed CD27⁻ γδ T (γδ²⁷⁻-17) cells. We found selective augmentation of Vγ4⁺ γδ²⁷⁻ cells with higher IL-17 production in KLF10-deficient mice. Surprisingly, KLF10-deficient CD127^hi Vγ4⁺ γδ²⁷⁻-17 cells expressed higher levels of CD5 than their wild-type counterparts, with hyper-responsiveness to cytokine, but not T-cell receptor, stimuli. Thymic maturation of Vγ4⁺ γδ²⁷⁻ cells was enhanced in newborn mice deficient in KLF10. Finally, a mixed bone marrow chimera study indicates that intrinsic KLF10 signaling is requisite to limit Vγ4⁺ γδ²⁷⁻-17 cells. Collectively, these findings demonstrate that KLF10 regulates thymic development of Vγ4⁺ γδ²⁷⁻ cells and their peripheral homeostasis at steady state.</p

Data_Sheet_2.PDF

<p>γδ T cells, known to be an important source of innate IL-17 in mice, provide critical contributions to host immune responses. Development and function of γδ T cells are directed by networks of diverse transcription factors (TFs). Here, we examine the role of the zinc finger TFs, Kruppel-like factor 10 (KLF10), in the regulation of IL-17-committed CD27⁻ γδ T (γδ²⁷⁻-17) cells. We found selective augmentation of Vγ4⁺ γδ²⁷⁻ cells with higher IL-17 production in KLF10-deficient mice. Surprisingly, KLF10-deficient CD127^hi Vγ4⁺ γδ²⁷⁻-17 cells expressed higher levels of CD5 than their wild-type counterparts, with hyper-responsiveness to cytokine, but not T-cell receptor, stimuli. Thymic maturation of Vγ4⁺ γδ²⁷⁻ cells was enhanced in newborn mice deficient in KLF10. Finally, a mixed bone marrow chimera study indicates that intrinsic KLF10 signaling is requisite to limit Vγ4⁺ γδ²⁷⁻-17 cells. Collectively, these findings demonstrate that KLF10 regulates thymic development of Vγ4⁺ γδ²⁷⁻ cells and their peripheral homeostasis at steady state.</p

Data_Sheet_4.PDF

<p>γδ T cells, known to be an important source of innate IL-17 in mice, provide critical contributions to host immune responses. Development and function of γδ T cells are directed by networks of diverse transcription factors (TFs). Here, we examine the role of the zinc finger TFs, Kruppel-like factor 10 (KLF10), in the regulation of IL-17-committed CD27⁻ γδ T (γδ²⁷⁻-17) cells. We found selective augmentation of Vγ4⁺ γδ²⁷⁻ cells with higher IL-17 production in KLF10-deficient mice. Surprisingly, KLF10-deficient CD127^hi Vγ4⁺ γδ²⁷⁻-17 cells expressed higher levels of CD5 than their wild-type counterparts, with hyper-responsiveness to cytokine, but not T-cell receptor, stimuli. Thymic maturation of Vγ4⁺ γδ²⁷⁻ cells was enhanced in newborn mice deficient in KLF10. Finally, a mixed bone marrow chimera study indicates that intrinsic KLF10 signaling is requisite to limit Vγ4⁺ γδ²⁷⁻-17 cells. Collectively, these findings demonstrate that KLF10 regulates thymic development of Vγ4⁺ γδ²⁷⁻ cells and their peripheral homeostasis at steady state.</p

Data_Sheet_5.PDF

<p>γδ T cells, known to be an important source of innate IL-17 in mice, provide critical contributions to host immune responses. Development and function of γδ T cells are directed by networks of diverse transcription factors (TFs). Here, we examine the role of the zinc finger TFs, Kruppel-like factor 10 (KLF10), in the regulation of IL-17-committed CD27⁻ γδ T (γδ²⁷⁻-17) cells. We found selective augmentation of Vγ4⁺ γδ²⁷⁻ cells with higher IL-17 production in KLF10-deficient mice. Surprisingly, KLF10-deficient CD127^hi Vγ4⁺ γδ²⁷⁻-17 cells expressed higher levels of CD5 than their wild-type counterparts, with hyper-responsiveness to cytokine, but not T-cell receptor, stimuli. Thymic maturation of Vγ4⁺ γδ²⁷⁻ cells was enhanced in newborn mice deficient in KLF10. Finally, a mixed bone marrow chimera study indicates that intrinsic KLF10 signaling is requisite to limit Vγ4⁺ γδ²⁷⁻-17 cells. Collectively, these findings demonstrate that KLF10 regulates thymic development of Vγ4⁺ γδ²⁷⁻ cells and their peripheral homeostasis at steady state.</p