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Novel biphasic role for lymphocytes revealed during resolving inflammation.

Rajakariar R, Lawrence T, Bystrom J, Hilliard M, Colville-Nash P, Bellingan G, Fitzgerald D, Yaqoob MM, Gilroy DW - Blood (2008)

Bottom Line: Acute inflammation is traditionally described as the influx of polymorphonuclear leukocytes (PMNs) followed by monocyte-derived macrophages, leading to resolution.To redress this we show, using lymphocyte-deficient RAG1(-/-) mice, that peritoneal T/B lymphocytes control PMN trafficking by regulating cytokine synthesis.Once inflammation ensues in normal mice, lymphocytes disappear in response to DP1 receptor activation by prostaglandin D(2).

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Medicine and Translational Therapeutics, William Harvey Research Institute, London, United Kingdom.

ABSTRACT
Acute inflammation is traditionally described as the influx of polymorphonuclear leukocytes (PMNs) followed by monocyte-derived macrophages, leading to resolution. This is a classic view, and despite subpopulations of lymphocytes possessing innate immune-regulatory properties, seldom is their role in acute inflammation and its resolution discussed. To redress this we show, using lymphocyte-deficient RAG1(-/-) mice, that peritoneal T/B lymphocytes control PMN trafficking by regulating cytokine synthesis. Once inflammation ensues in normal mice, lymphocytes disappear in response to DP1 receptor activation by prostaglandin D(2). However, upon resolution, lymphocytes repopulate the cavity comprising B1, natural killer (NK), gamma/delta T, CD4(+)/CD25(+), and B2 cells. Repopulating lymphocytes are dispensable for resolution, as inflammation in RAG1(-/-) and wild-type mice resolve uniformly. However, repopulating lymphocytes are critical for modulating responses to superinfection. Thus, in chronic granulomatous disease using gp91phox(-/-) mice, not only is resolution delayed compared with wild-type, but there is a failure of lymphocyte re-appearance predisposing to exaggerated immune responses upon secondary challenge that is rescued by resolution-phase lymphocytes. In conclusion, as lymphocyte repopulation is also evident in human peritonitis, we hereby describe a transition in T/B cells from acute inflammation to resolution, with a central role in modulating the severity of early onset and orchestrating responses to secondary infection.

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A summary of the scheme of events that occurs in acute inflammation with reference to lymphocyte trafficking. As inflammation ensues resident lymphocytes begin to disappear, with B1 cells clearing via draining lymphatics and the fate of CD3 cells remaining unclear at this stage. Once inflammation begins to resolve, lymphocytes repopulate the site of injury in a profile different to that in the naive state.
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Figure 5: A summary of the scheme of events that occurs in acute inflammation with reference to lymphocyte trafficking. As inflammation ensues resident lymphocytes begin to disappear, with B1 cells clearing via draining lymphatics and the fate of CD3 cells remaining unclear at this stage. Once inflammation begins to resolve, lymphocytes repopulate the site of injury in a profile different to that in the naive state.

Mentions: In summary, we report a biphasic role for lymphocytes during innate immune-mediated inflammation, summarized in Figure 5. The first phase controls PMN trafficking with lymphocytes then vacating the peritoneal cavity in response to PGD2 activating its DP1 receptor. The second phase is characterized by lymphocyte repopulation occurring after inflammation begins to resolve in a different proportion and profile to that of the naive state. Importantly, repopulating lymphocytes have no role in bringing about resolution, but protect against secondary infection.


Novel biphasic role for lymphocytes revealed during resolving inflammation.

Rajakariar R, Lawrence T, Bystrom J, Hilliard M, Colville-Nash P, Bellingan G, Fitzgerald D, Yaqoob MM, Gilroy DW - Blood (2008)

A summary of the scheme of events that occurs in acute inflammation with reference to lymphocyte trafficking. As inflammation ensues resident lymphocytes begin to disappear, with B1 cells clearing via draining lymphatics and the fate of CD3 cells remaining unclear at this stage. Once inflammation begins to resolve, lymphocytes repopulate the site of injury in a profile different to that in the naive state.
© Copyright Policy - creativecommons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2602590&req=5

Figure 5: A summary of the scheme of events that occurs in acute inflammation with reference to lymphocyte trafficking. As inflammation ensues resident lymphocytes begin to disappear, with B1 cells clearing via draining lymphatics and the fate of CD3 cells remaining unclear at this stage. Once inflammation begins to resolve, lymphocytes repopulate the site of injury in a profile different to that in the naive state.
Mentions: In summary, we report a biphasic role for lymphocytes during innate immune-mediated inflammation, summarized in Figure 5. The first phase controls PMN trafficking with lymphocytes then vacating the peritoneal cavity in response to PGD2 activating its DP1 receptor. The second phase is characterized by lymphocyte repopulation occurring after inflammation begins to resolve in a different proportion and profile to that of the naive state. Importantly, repopulating lymphocytes have no role in bringing about resolution, but protect against secondary infection.

Bottom Line: Acute inflammation is traditionally described as the influx of polymorphonuclear leukocytes (PMNs) followed by monocyte-derived macrophages, leading to resolution.To redress this we show, using lymphocyte-deficient RAG1(-/-) mice, that peritoneal T/B lymphocytes control PMN trafficking by regulating cytokine synthesis.Once inflammation ensues in normal mice, lymphocytes disappear in response to DP1 receptor activation by prostaglandin D(2).

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Medicine and Translational Therapeutics, William Harvey Research Institute, London, United Kingdom.

ABSTRACT
Acute inflammation is traditionally described as the influx of polymorphonuclear leukocytes (PMNs) followed by monocyte-derived macrophages, leading to resolution. This is a classic view, and despite subpopulations of lymphocytes possessing innate immune-regulatory properties, seldom is their role in acute inflammation and its resolution discussed. To redress this we show, using lymphocyte-deficient RAG1(-/-) mice, that peritoneal T/B lymphocytes control PMN trafficking by regulating cytokine synthesis. Once inflammation ensues in normal mice, lymphocytes disappear in response to DP1 receptor activation by prostaglandin D(2). However, upon resolution, lymphocytes repopulate the cavity comprising B1, natural killer (NK), gamma/delta T, CD4(+)/CD25(+), and B2 cells. Repopulating lymphocytes are dispensable for resolution, as inflammation in RAG1(-/-) and wild-type mice resolve uniformly. However, repopulating lymphocytes are critical for modulating responses to superinfection. Thus, in chronic granulomatous disease using gp91phox(-/-) mice, not only is resolution delayed compared with wild-type, but there is a failure of lymphocyte re-appearance predisposing to exaggerated immune responses upon secondary challenge that is rescued by resolution-phase lymphocytes. In conclusion, as lymphocyte repopulation is also evident in human peritonitis, we hereby describe a transition in T/B cells from acute inflammation to resolution, with a central role in modulating the severity of early onset and orchestrating responses to secondary infection.

Show MeSH
Related in: MedlinePlus