CD4+VEGFR1HIGH T cell as a novel Treg subset regulates inflammatory bowel disease in lymphopenic mice

Shin, Jin Young; Yoon, Ina; Lim, Jong Hyung; Shin, Jong Son; Nam, Hyun-Yeol; Kim, Yong Hee; Cho, Hyoung-Soo; Hong, So Hee; Kim, Jung-Sik; Lee, Won Woo; Park, Chung Gyu

doi:10.1038/cmi.2015.71

Cited by 9 publications

(7 citation statements)

References 67 publications

(70 reference statements)

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“…Further, CD4 + VEGFR1 high T cells are able to suppress the proliferation of CD4 + CD25 neg T cell as efficiently as CD4 + CD25 high natural Tregs in a contact-independent manner by soluble factor-mediated induction of apoptosis, in a model of lymphopenic mice. These findings strengthen the importance of the role of CD4 + VEGFR1 high T cells in the maintenance of immune homeostasis and are additional evidence for the link between the effects of VEGFR1 mediated signaling and the inadequate immune response in tumors [200] (Figure 2).…”

Section: Multifaceted Role Plgf/vegfr-1/nrp1/nrp2 Signaling In Antsupporting

confidence: 68%

Multifaceted Role of the Placental Growth Factor (PlGF) in the Antitumor Immune Response and Cancer Progression

Albonici

Giganti

Modesti

et al. 2019

IJMS

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The sharing of molecules function that affects both tumor growth and neoangiogenesis with cells of the immune system creates a mutual interplay that impairs the host’s immune response against tumor progression. Increasing evidence shows that tumors are able to create an immunosuppressive microenvironment by recruiting specific immune cells. Moreover, molecules produced by tumor and inflammatory cells in the tumor microenvironment create an immunosuppressive milieu able to inhibit the development of an efficient immune response against cancer cells and thus fostering tumor growth and progression. In addition, the immunoediting could select cancer cells that are less immunogenic or more resistant to lysis. In this review, we summarize recent findings regarding the immunomodulatory effects and cancer progression of the angiogenic growth factor namely placental growth factor (PlGF) and address the biological complex effects of this cytokine. Different pathways of the innate and adaptive immune response in which, directly or indirectly, PlGF is involved in promoting tumor immune escape and metastasis will be described. PlGF is important for building up vascular structures and functions. Although PlGF effects on vascular and tumor growth have been widely summarized, its functions in modulating the immune intra-tumoral microenvironment have been less highlighted. In agreement with PlGF functions, different antitumor strategies can be envisioned.

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Section: Multifaceted Role Plgf/vegfr-1/nrp1/nrp2 Signaling In Antsupporting

confidence: 68%

Multifaceted Role of the Placental Growth Factor (PlGF) in the Antitumor Immune Response and Cancer Progression

Albonici

Giganti

Modesti

et al. 2019

IJMS

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“…demonstrated in mouse model that engagement of T‐cell VEGFR‐1 with its ligand (VEGF) induced IL‐10 in isolated spleen T cells and CD4 + T cell clone. 29 Our data are in agreement with these results and demonstrate that VEGFR‐1 signaling enhances IL‐10 production in human T lymphocytes including both CD4 + and CD8 + subsets. Notably, VEGFR‐1 binding with VEGF in Shin's study did not inhibit T cell proliferation.…”

Section: Discussionsupporting

confidence: 91%

“…using goat anti‐mouse VEGFR‐1 polyclonal Abs reported that activated T cells transcribed mRNA of VEGFR‐1 and VEGFR‐2, but expressed only VEGFR‐1 28 . Later these authors reconfirmed the expression of VEGFR‐1 utilizing mAbs and identified a novel subset of regulatory CD4 + T cells with high expression of VEGFR‐1 in peripheral blood 29 . Voron et al.…”

Section: Discussionmentioning

confidence: 99%

Binding of the placental growth factor to VEGF receptor type 1 modulates human T cell functions

Леплина

Smetanenko

Тихонова

et al. 2020

Journal of Leukocyte Biology

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The immunosuppressive properties of vascular endothelial growth factors (VEGFs) suggest a new role of angiogenic factors in T cell modulation in cancer and pregnancy. Most of VEGF effects on T cells are mediated through the VEGF receptor type 2 (VEGFR‐2). This study aims to investigate the role of placental growth factor (PlGF) as a selective VEGFR‐1 ligand in the modulation of human T cells functions. For this, PBMCs from healthy donors were stimulated with anti‐CD3 mAbs (a‐CD3) or Concanavalin A (ConA) in the absence or presence of PlGF and assessed for T cell proliferation, IL‐10 production, programmed cell death, and the expression of inhibitory receptors (PD‐1, CTLA‐4, TIM‐3) using radiometric (3H‐thymidine incorporation) and FACS analysis. We showed that most T cells in freshly isolated PBMCs lacked VEGFR‐1. However, activation with a‐CD3 or ConA strongly increased the percentages of VEGFR‐1 expressing CD4+ and CD8+ T cells. PlGF in a wide dose range suppressed PBMC cell proliferation, inhibiting both CD4+ and CD8+ T cells. Blockade of VEGFR‐1, but not VEGFR‐2 with neutralizing Abs completely abolished the suppressive effect of PlGF. Furthermore, we found that treatment with PlGF up‐regulated IL‐10 production in CD4+ and CD8+ T cells, promoted CD8+ T cells apoptosis and enhanced the expression of inhibitory receptors (PD‐1 and TIM‐3) on activated T cells. Our in vitro findings suggest the involvement of PlGF/VEGFR‐1 signaling in the modulation of T cell responses in a‐CD3‐stimulated PBMCs.

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“…Tonsillectomy involves the depletion of Treg cells in tonsils and alters the intestinal immune environment through its mucosa‐associated lymphoid system 59 . Tonsillectomy was a CD risk factor in Western and Eastern populations.…”

Section: Discussionmentioning

confidence: 99%

Systematic review with meta‐analysis: environmental and dietary differences of inflammatory bowel disease in Eastern and Western populations

Zhao

Feng

Ben‐Horin

et al. 2021

Aliment Pharmacol Ther

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Summary Background While the incidence of inflammatory bowel disease (IBD) has stabilised in the West, it is still increasing in several newly industrialised countries. Aims To investigate whether the environmental and dietary risk factors for IBD differ between Eastern and Western populations Methods We systematically searched PubMed, Embase, and Web of Science for studies published from inception through June 30, 2020. Data were pooled using a random effects model. Results Overall, 255 studies were assessed. We identified 25 risk factors for IBD, seven of which were noted in both Eastern and Western populations: family history of Crohn's disease [CD] or ulcerative colitis [UC], former smoking (CD/UC), smoking (CD), appendicectomy (CD), tonsillectomy (CD), meat and meat products (CD), and vitamin D deficiency (UC). The remaining factors, including urban living, current smoking, antibiotics, oral contraceptives, caesarean section, isotretinoin, total energy, fat, cholesterol, fatty acids and their sub‐classifications, eggs, and soft drinks, were associated with an increased risk of IBD in Western or Eastern populations only. We identified 21 protective factors for IBD, among which eight were common in the East and West: farm animals (CD/UC), Helicobacter pylori infection (CD/UC), multiple births (CD), physical activity (CD), history of breastfeeding (CD), pets (UC), current smoking (UC), and coffee intake (UC). Ten factors conferred protection against IBD in Western populations only, whereas eight factors conferred protection against IBD in Eastern populations only. Conclusions Numerous environmental and dietary factors influenced the development of IBD in both Western and Eastern populations, whereas certain factors influenced IBD risk differently in these populations.

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CD4+VEGFR1HIGH T cell as a novel Treg subset regulates inflammatory bowel disease in lymphopenic mice

Cited by 9 publications

References 67 publications

Multifaceted Role of the Placental Growth Factor (PlGF) in the Antitumor Immune Response and Cancer Progression

Multifaceted Role of the Placental Growth Factor (PlGF) in the Antitumor Immune Response and Cancer Progression

Binding of the placental growth factor to VEGF receptor type 1 modulates human T cell functions

Systematic review with meta‐analysis: environmental and dietary differences of inflammatory bowel disease in Eastern and Western populations

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