Immunological function of Blimp-1 in dendritic cells and relevance to autoimmune diseases

Kim, Sun Jung

doi:10.1007/s12026-015-8694-5

Cited by 30 publications

(20 citation statements)

References 80 publications

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“…Blimp1 is a transcriptional regulator that is crucial for terminal differentiation of several lineages. Its role in the immune system was first described in B cells (revised in 1 ), but more recent studies also uncovered non-redundant roles for Blimp1 in myeloid cells 33 , 34 and T lymphocytes 5 – 8 , 11 – 13 , 25 , 32 . Mice with T-cell specific deletion of Blimp1 (Blimp1CKO) spontaneously develop severe intestinal inflammation 6 and can be potentially useful as an experimental model to study T cell-mediate intestinal pathology however, the mechanisms underlying disease development in these mice are not fully understood.…”

Section: Discussionmentioning

confidence: 99%

Differential regulation of Effector and Regulatory T cell function by Blimp1

Bankoti¹,

Ogawa²,

Nguyen³

et al. 2017

Sci Rep

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The transcriptional regulator Blimp1 plays crucial roles in controlling terminal differentiation in several lineages. In T cells, Blimp1 is expressed in both effector (Teff) and regulatory (Treg) cells, and mice with T cell-specific deletion of Blimp1 (Blimp1CKO mice) spontaneously develop severe intestinal inflammation, indicating a crucial role for Blimp1 in T cell homeostasis regulation. Blimp1 has been shown to function as a direct activator of the Il10 gene and although its requirement for IL10 expression has been demonstrated in both Treg and Teff cells under inflammatory conditions, the intrinsic requirement of Blimp1 for homeostatic maintenance of these T cell subsets had not been investigated. Using mice with Foxp3+ Treg-cell specific deletion of Blimp1 and other approaches, here we show that Foxp3+ Treg cell-intrinsic expression of Blimp1 is required to control Treg and Teff cells homeostasis but, unexpectedly, it is dispensable to prevent development of severe spontaneous intestinal inflammation. In addition, we show that Blimp1 controls common and unique aspects of Treg and Teff cell function by differentially regulating gene expression in these T cell subsets. These findings document previously unappreciated aspects of Blimp1’s role in T cell biology and shed light on the intricate mechanisms regulating Treg and Teff cell function.

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Section: Discussionmentioning

confidence: 99%

Differential regulation of Effector and Regulatory T cell function by Blimp1

Bankoti¹,

Ogawa²,

Nguyen³

et al. 2017

Sci Rep

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“…Prdm1 is the key regulator of primordial germ cells (PGCs) in the embryo39 but it is also linked to stem cell pluripotency and maturation in non-germline cells404142434445464748. Here it was not a specific marker of the germline as it could be detected in dermal fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

“…Only Prdm1 and Iftm3 , often regarded as germline markers 38 , were present in freshly isolated ovarian cells following FACS with DDX4 C25 antibody. Prdm1 is the key regulator of primordial germ cells (PGCs) in the embryo 39 but it is also linked to stem cell pluripotency and maturation in non-germline cells 40 41 42 43 44 45 46 47 48 . Here it was not a specific marker of the germline as it could be detected in dermal fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

FACS-sorted putative oogonial stem cells from the ovary are neither DDX4-positive nor germ cells

Zarate-Garcia

Lane

Merriman

et al. 2016

Sci Rep

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Whether the adult mammalian ovary contains oogonial stem cells (OSCs) is controversial. They have been isolated by a live-cell sorting method using the germ cell marker DDX4, which has previously been assumed to be cytoplasmic, not surface-bound. Furthermore their stem cell and germ cell characteristics remain disputed. Here we show that although OSC-like cells can be isolated from the ovary using an antibody to DDX4, there is no good in silico modelling to support the existence of a surface-bound DDX4. Furthermore these cells when isolated were not expressing DDX4, and did not initially possess germline identity. Despite these unremarkable beginnings, they acquired some pre-meiotic markers in culture, including DDX4, but critically never expressed oocyte-specific markers, and furthermore were not immortal but died after a few months. Our results suggest that freshly isolated OSCs are not germ stem cells, and are not being isolated by their DDX4 expression. However it may be that culture induces some pre-meiotic markers. In summary the present study offers weight to the dogma that the adult ovary is populated by a fixed number of oocytes and that adult de novo production is a rare or insignificant event.

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“…Genetic factors in the context of environmental triggers are thought to play important roles (4). Some identified risk gene loci for SLE include BLIMP1, IRF5 and C1q (5)(6)(7)(8). C1q binds to opsonized cellular debris to mediate the clearance of dead and dying cells (9)(10)(11).…”

Section: Systemic Lupus Erythematosus (Sle)mentioning

confidence: 99%

HMGB1 in Systemic Lupus Erythematosus

2020

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The high-mobility group box 1 (HMGB1) has been shown to exert proinflammatory effects on many cells of the innate immune system. Originally identified as a nuclear protein, HMGB1 has been found to play an important role in mediating inflammation when released from apoptotic or necrotic cells as a damage-associated molecular pattern (DAMP). Systemic lupus erythematosus (SLE) is a disease of non-resolving inflammation, characterized by the presence of autoantibodies and systemic inflammation involving multiple organ systems. SLE patients have impaired clearance of apoptotic debris, which releases HMGB1 and other DAMPs extracellularly. HMGB1 activity is implicated in multiple disease phenotypes in SLE, including lupus nephritis and neuropsychiatric lupus. Elucidating the various properties of HMGB1 in SLE provides a better understanding of the disease and opens up new opportunities for designing potential therapeutics.

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Immunological function of Blimp-1 in dendritic cells and relevance to autoimmune diseases

Cited by 30 publications

References 80 publications

Differential regulation of Effector and Regulatory T cell function by Blimp1

Differential regulation of Effector and Regulatory T cell function by Blimp1

FACS-sorted putative oogonial stem cells from the ovary are neither DDX4-positive nor germ cells

HMGB1 in Systemic Lupus Erythematosus

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