T Regulatory Cells Support Plasma Cell Populations in the Bone Marrow

Zaretsky, Arielle Glatman; Konradt, Christoph; Dépis, Fabien; Wing, James B.; Goenka, Radhika; Atria, Daniela Gómez; Silver, Jonathan S.; Cho, Sunglim; Wolf, Amaya I.; Quinn, William J.; Engiles, Julie B.; Brown, Dorothy Cimino; Beiting, Daniel; Erikson, Jan; Allman, David; Cancro, Michael P.; Sakaguchi, Shimon; Lu, Li-Fan; Benoist, Christophe; Hunter, Christopher A.

doi:10.1016/j.celrep.2017.01.067

Cited by 87 publications

(63 citation statements)

References 62 publications

(91 reference statements)

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“…Evidently additional work is needed in this area. Interestingly, recent data indicate that depletion of regulatory T cells (Tregs) from the BM also causes loss of plasma cells (89). In this regard, past work suggests that Tregs protect HSCs from inflammatory signals with the potential of disrupting hematopoiesis (90).…”

Section: Introductionmentioning

confidence: 99%

“…To begin, if plasma cells can indeed use APRIL or BLyS interchangeably (70), because BLyS is by and large a systemic cytokine (96), it is difficult to imagine scenarios where plasma cells require life-long residence in physical APRIL-rich survival niches, in the BM or elsewhere. Second, it should be emphasized that, whereas systemic inflammatory responses can severely deplete BM plasma cell pools (89, 97), likely through temporary loss of CXCL12 expression (98), there is also evidence that such cells can relocate into alternative CXCL12-rich tissues (78). This general assertion also applies to experiments wherein integrin blockade led to transient loss of BM plasma cells (64).…”

Section: Introductionmentioning

confidence: 99%

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Here, There, and Anywhere? Arguments for and against the Physical Plasma Cell Survival Niche

Wilmore

Allman

2017

The Journal of Immunology

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To maintain antibody titers individual plasma cells must survive for extended periods, perhaps even for the life of the host. While it is clear that plasma cell survival requires cell extrinsic signals, the nature and source of these signals remains open for debate. It is commonly postulated that plasma cells only gain access to these signals within specialized regulatory microenvironments, or niches, in the bone marrow or in the gut. Here we discuss current concepts and information surrounding plasma cell survival niches, and consider two opposing models to explain long-term serologic immunity.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Here, There, and Anywhere? Arguments for and against the Physical Plasma Cell Survival Niche

Wilmore

Allman

2017

The Journal of Immunology

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“…These long‐lived cells migrate into the BM through the CXCL12/CXCR4 axis forming a Treg cell reservoir . In the BM, Treg cells have been shown not only to regulate the niche compartment – and thereby influence B‐cell differentiation – but also to support maintenance of long‐lived plasma cells . Interestingly, a recent report suggests that niche Treg cells may be distinct from peripheral Treg cells by their high expression of the HSC marker CD150 and their capacity to release adenosine into their local environment, which in turn reduces oxidative stress in HSC .…”

Section: Fatty Acids In the Bone Marrow To Support Long‐lived Immune mentioning

confidence: 99%

Local exchange of metabolites shapes immunity

2018

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SummaryImmune cell differentiation and function depend on metabolic changes for the provision of energy and metabolites. Consequently, cellular metabolism relies on the availability of micronutrients such as vitamins and energy‐rich sources including amino acids and fatty acids. The bone marrow controls the continuous production of blood cells and is thereby reliant on the sophisticated interplay of progenitor and mature immune cells with its stromal microenvironment. The significance of stromal subsets in immunopoiesis is undisputed; however, our current knowledge is limited to their role in the production and secretion of a variety of soluble proteins such as cytokines. In contrast, the role of the haematopoietic niche in controlling and providing nutrients such as fatty acids, amino acids and vitamins, which are required for immune cell differentiation and function, remains largely elusive. In this review, we summarize the current understanding of local nutritional exchange and control between immune and stromal cells in peripheral tissue and, when it is known, in the bone marrow. The parallels found between peripheral tissues and bone marrow stroma raises the question of how local metabolism is capable of influencing haematopoiesis and immunopoiesis. A better understanding of the local exchange of nutrients in the bone marrow can be used to improve immune cell formation during ageing, after haematopoietic stem cell transplantation and during immune challenge.

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“…The spleen is an additional key site of Treg activity and MPM has also been useful in investigating the actions of Tregs in this organ 20 . Previous work had demonstrated that treatment with anti‐CD45RB induced allograft tolerance via a Treg‐dependent mechanism 21 .…”

Section: Imaging Regulatory T Cells In Secondary Lymphoid Organsmentioning

confidence: 99%

“…More recently, MPM was used to investigate the mechanisms of plasma cell survival in the bone marrow 20 . Imaging the bone marrow of the skull bone, Tregs were found to co‐localise with plasma cells in extravascular endosteal niches.…”

Section: Imaging Regulatory T Cells In the Peripherymentioning

confidence: 99%

Viewing immune regulation as it happens: in vivo imaging for investigation of regulatory T‐cell function

Hickey

Chow

2017

Immunol Cell Biol

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Regulatory T cells (Tregs) play indispensable roles in the immune system, in limiting excessive or inappropriate immune and inflammatory responses. They achieve this function via effects on other immune cells in the secondary lymphoid system, and in peripheral locations such as skin, gut and bone marrow. As for the more extensively studied cellular players in the immune system, particularly dendritic cells and conventional T cells, in vivo imaging of Tregs via two-photon (or multiphoton) microscopy (MPM) has been central to the development of understanding how these cells function. In this brief review, we will describe the studies that have utilised MPM to examine Treg behaviour in vivo. These studies have investigated Treg behaviour in lymph nodes and spleen, as well as in peripheral organs such as skin, small intestine and bone marrow. The findings from these experiments underline how assumptions made about Treg function based on results of in vitro experiments are often not supported by direct visualisation of these cells in their normal in vivo settings. Together this work reveals that only via MPM analysis can Treg function be investigated in the complicated multicellular environments where conventional T cells, antigen-presenting cells and other potential cellular targets of Tregs are present with each undergoing their own specific actions.

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T Regulatory Cells Support Plasma Cell Populations in the Bone Marrow

Cited by 87 publications

References 62 publications

Here, There, and Anywhere? Arguments for and against the Physical Plasma Cell Survival Niche

Here, There, and Anywhere? Arguments for and against the Physical Plasma Cell Survival Niche

Local exchange of metabolites shapes immunity

Viewing immune regulation as it happens: in vivo imaging for investigation of regulatory T‐cell function

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