Foxp4 Is Dispensable for T Cell Development, but Required for Robust Recall Responses

Wiehagen, Karla R.; Corbo-Rodgers, Evann; Li, Shanru; Staub, Elizabeth; Hunter, Christopher A.; Morrisey, Edward E.

doi:10.1371/journal.pone.0042273

Cited by 36 publications

(28 citation statements)

References 35 publications

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“…Wiehagen et al found that FOXP4 is expressed in immature thymocytes and mature T lymphocyte subsets and it is dispensable for T cell development. However, FOXP4 is required for normal T cell cytokine robust recall responses (28). In addition, Long et al successfully replicated the association of rs1983891 (FOXP4) with prostate cancer and provide further support for association of the FOXP4 with prostate cancer in Eastern Asian populations (29).…”

Section: Discussionmentioning

confidence: 97%

Overexpression of long non-coding RNA MFI2 promotes cell proliferation and suppresses apoptosis in human osteosarcoma

Yin

Ding

et al. 2016

Oncology Reports

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The long non-coding RNA MFI2 antisense RNA is overexpressed in human cancer tissues and its increased expression is associated with occurrence and metastasis of cancer. However, the underlying mechanism in evolution and progression of human osteosarcoma is not well known. In the present study, we aimed to evaluate the molecular mechanism of lncRNA MFI2 in promoting osteosarcoma cell proliferation and suppressing apoptosis. We found that the lncRNA MFI2 was significantly overexpressed in human osteosarcoma tissues. Knockdown of lncRNA MFI2 expression suppressed MG63 and SAOS-2 cell proliferation, migration and invasion, and induced cell apoptosis. Furthermore, the expression of forkhead box P4 (FOXP4) was significantly increased and it was positively associated with lncRNA MFI2 expression in tumor tissues. In addition, knockdown of FOXP4 expression by RNA interference strategy inhibited osteosarcoma cell proliferation, migration and invasion, and promoted cell apoptosis. All the results indicated lncRNA MFI2 could promote proliferation and migration of osteosarcoma cells by regulating FOXP4 expression, which suggested critical roles of lncRNA MFI2 and FOXP4 in occurrence and development of human osteosarcoma.

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Section: Discussionmentioning

confidence: 97%

Overexpression of long non-coding RNA MFI2 promotes cell proliferation and suppresses apoptosis in human osteosarcoma

Yin

Ding

et al. 2016

Oncology Reports

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“…FoxM1 appears to be important for T cell proliferation and impaired FoxM1 expression might diminish the proliferative potential of FoxO1−/− memory CD8 T cells (47). Loss of Foxp4 has been reported to impair cytokine production by LCMV-specific CD4 T cells (48), but the role of Foxp4 in regulating CD8 T cell memory is yet to be determined. The reduced recall response of FoxO1−/− memory CD8 T cells is also associated with diminished levels of cyclins (A2, D1 and F) and increased expression of anti-proliferative cyclin-dependent kinase inhibitors (p15 INK4B , p18 INK4c and p57 Kip2 ) (Table 1).…”

Section: Discussionmentioning

confidence: 99%

FoxO1 Controls Effector-to-Memory Transition and Maintenance of Functional CD8 T Cell Memory

Tejera

Kim

Sullivan

et al. 2013

The Journal of Immunology

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During a T cell response, naïve CD8 T cells differentiate into effector cells. Subsequently, a subset of effector cells termed memory precursor effector cells (MPECs) further differentiates into functionally mature memory CD8 T cells. The transcriptional network underlying this carefully scripted process is not well understood. Here, we report that the transcription factor FoxO1 plays an integral role in facilitating effector to memory transition and functional maturation of memory CD4 and CD8 T cells. We find that FoxO1 is not required for differentiation of effector cells, but in the absence of FoxO1, memory CD8 T cells displayed features of senescence and progressive attrition in polyfunctionality, which in turn led to impaired recall responses and poor protective immunity. These data suggest that FoxO1 is essential for maintenance of functional CD8 T cell memory and protective immunity. Under competing conditions in bone marrow chimeric mice, FoxO1-deficiency did not perturb clonal expansion or effector differentiation. Instead, FoxO1-deficient MPECs failed to survive and form memory CD8 T cells. Mechanistically, FoxO1 deficiency perturbed the memory CD8 T-cell transcriptome, characterized by pronounced alterations in the expression of genes that encode transcription factors (including Tcf7), effector molecules, cell cycle regulators and proteins that regulate fatty acid, purine and pyramidine metabolism and mitochondrial functions. We propose that FoxO1 is a key regulator that reprograms and steers the differentiation of effector cells to functionally competent memory cells. These findings have provided fundamental insights into the mechanisms that regulate the quality of CD8 T-cell memory to intracellular pathogens.

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“… 47 Rs1983891 was located in intron 2 of FOXP4 (forkhead box P4), which is expressed in both thymocytes and peripheral CD4 (+) and CD8 (+) T-cells and is necessary for normal T-cell cytokine recall responses to antigen following pathogenic infection. 51 …”

Section: Geneticsmentioning

confidence: 99%

Prostate cancer in East Asia: evolving trend over the last decade

Zhu

Wang

et al. 2015

Asian J Androl

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Prostate cancer is now becoming an emerging health priority in East Asia. Most of our current knowledge on Prostate cancer has been generated from studies conducted in Western population; however, there is considerable heterogeneity of Prostate cancer between East and West. In this article, we reviewed epidemiologic trends, risk factors, disease characteristics and management of Prostate cancer in East Asian population over the last decade. Growing evidence from East Asia suggests an important role of genetic and environmental risk factors interactions in the carcinogenesis of Prostate cancer. Exposure to westernized diet and life style and improvement in health care in combination contribute substantially to the increasing epidemic in this region. Diagnostic and treatment guidelines in East Asia are largely based on Western knowledge. Although there is a remarkable improvement in the outcome over the last decade, ample evidence suggests an inneglectable difference in diagnostic accuracy, treatment efficacy and adverse events between different populations. The knowledge from western countries should be calibrated in the Asian setting to provide a better race-based treatment approach. In this review, we intend to reveal the evolving trend of Prostate cancer in the last decade, in order to gain evidence to improve Prostate cancer prevention and control in East Asia.

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Foxp4 Is Dispensable for T Cell Development, but Required for Robust Recall Responses

Cited by 36 publications

References 35 publications

Overexpression of long non-coding RNA MFI2 promotes cell proliferation and suppresses apoptosis in human osteosarcoma

Overexpression of long non-coding RNA MFI2 promotes cell proliferation and suppresses apoptosis in human osteosarcoma

FoxO1 Controls Effector-to-Memory Transition and Maintenance of Functional CD8 T Cell Memory

Prostate cancer in East Asia: evolving trend over the last decade

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