Innate Immune Cell CD45 Regulates Lymphopenia-Induced T Cell Proliferation

Saunders, Amy E.; Shim, Yaein Amy; Johnson, Pauline

doi:10.4049/jimmunol.1302681

Cited by 7 publications

(5 citation statements)

References 45 publications

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“…The enrichment of DMGs into the glycan synthesis pathway may be related to the regulation of pathogen recognition. At the same time, immune-related DMGs, such as VAV3 , PLCG2 , TEC and PTPRC participated in multiple immune pathways ( Miller and Berg, 2002 ; Tybulewicz, 2005 ; Saunders et al, 2014 ; Magno et al, 2019 ). Most of these genes act on adaptive immunity and are involved in the development and activation of T cells, which may be related to the stronger cellular immunity of the wildness training pandas mentioned in transcriptome analysis.…”

Section: Discussionmentioning

confidence: 99%

Whole genome bisulfite sequencing reveals DNA methylation roles in the adaptive response of wildness training giant pandas to wild environment

Jie

Wu²,

Yang³

et al. 2022

Front. Genet.

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DNA methylation modification can regulate gene expression without changing the genome sequence, which helps organisms to rapidly adapt to new environments. However, few studies have been reported in non-model mammals. Giant panda (Ailuropoda melanoleuca) is a flagship species for global biodiversity conservation. Wildness and reintroduction of giant pandas are the important content of giant pandas’ protection. However, it is unclear how wildness training affects the epigenetics of giant pandas, and we lack the means to assess the adaptive capacity of wildness training giant pandas. We comparatively analyzed genome-level methylation differences in captive giant pandas with and without wildness training to determine whether methylation modification played a role in the adaptive response of wildness training pandas. The whole genome DNA methylation sequencing results showed that genomic cytosine methylation ratio of all samples was 5.35%–5.49%, and the methylation ratio of the CpG site was the highest. Differential methylation analysis identified 544 differentially methylated genes (DMGs). The results of KEGG pathway enrichment of DMGs showed that VAV3, PLCG2, TEC and PTPRC participated in multiple immune-related pathways, and may participate in the immune response of wildness training giant pandas by regulating adaptive immune cells. A large number of DMGs enriched in GO terms may also be related to the regulation of immune activation during wildness training of giant pandas. Promoter differentially methylation analysis identified 1,199 genes with differential methylation at promoter regions. Genes with low methylation level at promoter regions and high expression such as, CCL5, P2Y13, GZMA, ANP32A, VWF, MYOZ1, NME7, MRPS31 and TPM1 were important in environmental adaptation for wildness training giant pandas. The methylation and expression patterns of these genes indicated that wildness training giant pandas have strong immunity, blood coagulation, athletic abilities and disease resistance. The adaptive response of giant pandas undergoing wildness training may be regulated by their negatively related promoter methylation. We are the first to describe the DNA methylation profile of giant panda blood tissue and our results indicated methylation modification is involved in the adaptation of captive giant pandas when undergoing wildness training. Our study also provided potential monitoring indicators for the successful reintroduction of valuable and threatened animals to the wild.

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Section: Discussionmentioning

confidence: 99%

Whole genome bisulfite sequencing reveals DNA methylation roles in the adaptive response of wildness training giant pandas to wild environment

Jie

Wu²,

Yang³

et al. 2022

Front. Genet.

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“…A recent study demonstrated that, upon the transfer of polyclonal CD45 þ / þ T cells into naive CD45RAG À / À and RAG À / À mice, there was reduced lymphopenia-induced proliferation of the transferred T cells in CD45RAG À / À mice, resulting in lower frequency and number of CD45 þ / þ T cells in the spleen and peripheral lymph nodes on day 7 after transfer. 7 However, upon inflammation induced by DSS, there was no significant difference in T-cell frequency or number in the spleen between CD45RAG À / À and RAG À / À mice (see Supplementary Figure S7), suggesting that lymphopenia-induced proliferation is not a contributing factor to the reduction of colon T cells observed in CD45RAG À / À mice. In addition, there was no significant increase in the percentage of Foxp3 þ T cells within CD4 þ or CD8 þ T cells in the spleen, mLNs, and LP of the CD45RAG À / À mice (see Supplementary Figure S8), indicating that increased numbers of Tregs were not the reason for the reduced colitis observed in CD45RAG À / À mice.…”

Section: Cd45 Helps Promote Ra Production By Dcs In the Mlns In Dss-imentioning

confidence: 91%

“…CD45E6 À / À have significantly reduced numbers of T cells in the spleen and periphery and CD45E9 À / À mice have even less T cells compared with wild-type (WT) mice. 4,5,7 Although most leukocytes are negative for CD45, in the CD45E6 À / À mice, a small percentage of T cells express low levels of the CD45RB isoform, whereas in CD45E9 À / À mice all the leukocytes, including the T cells, are CD45 null. The CD45E6 À / À T cells express higher levels of LFA-1 and CD44, 8 and we have found increased levels of LFA-1 on CD45E9 À / À T cells (unpublished data).…”

Section: Introductionmentioning

confidence: 99%

CD45 regulates GM-CSF, retinoic acid and T-cell homing in intestinal inflammation

et al. 2016

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CD45 is a leukocyte-specific tyrosine phosphatase important for T-cell development, and as a result, CD45 mice have substantially reduced numbers of T cells. Here we show that, upon dextran sodium sulfate (DSS)-induced colitis, CD45 mice have equivalent intestinal pathology and T-cell numbers in their colon as C57BL/6 mice and show enhanced weight loss. CD45 mice have a greater percentage of α4β7 T cells prior to and after colitis and an increased percentage of T cells producing inflammatory cytokines in the inflamed colon, suggesting that CD45 effector T cells preferentially home to the intestine. In DSS-induced colitis in CD45RAG mice lacking an adaptive immune system, CD45 was required for optimal granulocyte-macrophage colony-stimulating factor (GM-CSF) and retinoic acid (RA) production by innate immune cells. Addition of CD45 T cells led to greater weight loss in the RAG mice compared with CD45RAG mice that correlated with reduced α4β7 T cells and lower recruitment to the colon of CD45RAG mice in DSS-induced colitis. Addition of exogenous GM-CSF to CD45RAG mice rescued RA production, increased colonic T-cell numbers, and increased weight loss. This demonstrates opposing effects of CD45 in innate and adaptive immune cells in proinflammatory responses and the expression of the gut-homing molecule, α4β7.

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“…In general, the mechanisms of regulation of CD45 expression have been poorly studied, and there is no evidence of ligand-induced activation of CD45. It is possible that CD45 is permanently active, and that it causes dephosphorylation of Src family kinases, maintaining them in a working, non-phosphorylated state [51].…”

Section: Discussionmentioning

confidence: 99%

Effects of pregnancy-specific β-1-glycoprotein on the helper T-cell response

Тимганова

Бочкова

Khramtsov

et al. 2019

ARCH BIOL SCI BELGRA

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Pregnancy-specific β-1-glycoproteins (PSGs) are capable of regulating innate and adaptive immunity. As fetal antigens circulate in the blood of pregnant women, it is of particular interest to reveal the effects of PSGs on the differentiation of memory T cells in the context of maternal-fetal tolerance formation. We studied if, native PSG preparation affects helper T-cell proliferation, the frequencies of CD4 + CD45R0 + , CD4 + CD45RA + , CD4 + CD45RA + CD45R0 + cells, naive CD45RA + CD45R0-CD62L + cells (NAIVE), central memory CD45RA-CD45R0 + CD62L + cells (TCM), effector memory helper T cells (CD45RA-CD45R0 + CD62L-(TEM) and CD45RA + CD45R0-CD62Lcells (TEMRA), together with IL-4 and IFN-γ production by all СD4 + T cells. The suppressive effect of PSG on helper T-cell proliferation was established. It was found that PSG does not influence the frequencies of CD45RA + and CD45R0 + cells, while it decreased the percentage of CD45RA + CD45R0 + cells. PSG increased the percentage of NAIVE cells in culture, and prevented the conversion of these cells into TEMRA, without affecting the levels of TCM and TEM. In addition, PSG lowered the amount of IL-4 and IFN-γ in the supernatants of helper T-cell cultures. As TEMRA exhibit cytotoxic activity that is unfavorable during pregnancy, the revealed PSG effects may play a fetoprotective role in vivo.

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Innate Immune Cell CD45 Regulates Lymphopenia-Induced T Cell Proliferation

Cited by 7 publications

References 45 publications

Whole genome bisulfite sequencing reveals DNA methylation roles in the adaptive response of wildness training giant pandas to wild environment

Whole genome bisulfite sequencing reveals DNA methylation roles in the adaptive response of wildness training giant pandas to wild environment

CD45 regulates GM-CSF, retinoic acid and T-cell homing in intestinal inflammation

Effects of pregnancy-specific β-1-glycoprotein on the helper T-cell response

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