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CD69 is the crucial regulator of intestinal inflammation: a new target molecule for IBD treatment?

Radulovic K, Niess JH - J Immunol Res (2015)

Bottom Line: However, recent work has indicated that CD69 plays an essential role for the regulation of inflammatory processes.Particularly, CD69 is highly expressed by lymphocytes at mucosal sites being constantly exposed to the intestinal microflora (one of the nature's most complex and most densely populated microbial habitats) and food antigens, while only a small number of circulating leukocytes express this molecule.In this review we will discuss the role of CD69 in mucosal tissue and consider CD69 as a potential target for the development of novel treatments of intestinal inflammation.

View Article: PubMed Central - PubMed

Affiliation: U1019, Team 7, Institut National de la Santé et de la Recherche Médicale (INSERM), 1 rue du Professeur Calmette, 59019 Lille, France ; Center for Infection and Immunity of Lille, Institut Pasteur de Lille, 1 rue du Professeur Calmette, 59019 Lille, France.

ABSTRACT
CD69 has been identified as an early activation marker of lymphocytes. However, recent work has indicated that CD69 plays an essential role for the regulation of inflammatory processes. Particularly, CD69 is highly expressed by lymphocytes at mucosal sites being constantly exposed to the intestinal microflora (one of the nature's most complex and most densely populated microbial habitats) and food antigens, while only a small number of circulating leukocytes express this molecule. In this review we will discuss the role of CD69 in mucosal tissue and consider CD69 as a potential target for the development of novel treatments of intestinal inflammation.

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Related in: MedlinePlus

The role of CD69 in mucosal immunity. Activation of intestinal CD4 T cell by antigen recognition, type I interferons (IFN-I), or by presence of intestinal microflora leads to the upregulation of CD69 expression on the cell surface. After binding a ligand, CD69 activates the intracellular pathways that result in decreased production of proinflammatory cytokines (IFN-γ, TNF-α, and IL-21) and chemokines (Ccl-1, Cxcl-10, and Ccl-19) and increased production of regulatory cytokine TGF-β1. If the CD4 T cell establishes a stable expression of CD69, this cell can differentiate into CD69+ regulatory T cell (Treg) or tissue resident memory T cell (TRM). Therefore, upregulation of CD69 leads to the decreased migration of activated CD4 T cells to the intestine and to the increased regulatory responses, which ensures the establishment of oral tolerance and the attenuation of colitis severity.
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fig3: The role of CD69 in mucosal immunity. Activation of intestinal CD4 T cell by antigen recognition, type I interferons (IFN-I), or by presence of intestinal microflora leads to the upregulation of CD69 expression on the cell surface. After binding a ligand, CD69 activates the intracellular pathways that result in decreased production of proinflammatory cytokines (IFN-γ, TNF-α, and IL-21) and chemokines (Ccl-1, Cxcl-10, and Ccl-19) and increased production of regulatory cytokine TGF-β1. If the CD4 T cell establishes a stable expression of CD69, this cell can differentiate into CD69+ regulatory T cell (Treg) or tissue resident memory T cell (TRM). Therefore, upregulation of CD69 leads to the decreased migration of activated CD4 T cells to the intestine and to the increased regulatory responses, which ensures the establishment of oral tolerance and the attenuation of colitis severity.

Mentions: CD69 has been for decades used as a simple marker of activated leukocytes without knowing any concrete role this receptor could play in the regulation of immune responses. The discovery that CD69 expression depends on the presence of the intestinal microflora opened new insight into the role CD69 has in immunity and inflammation in intestine. Induced by the specific antigen and/or intestinal microflora, CD69 regulates the essential processes such as the migration of lymphocytes, cytokine secretion, and generation of regulatory and memory T cells at the mucosal sites (Figure 3). CD69 directs the immune responses in the intestine toward the oral tolerance and regulatory responses (Figure 3) [48]. In vivo CD69 limited the intestinal inflammation proving to be one of the crucial negative regulators of the immune responses in the gut. The activation of CD69 induces tolerogenic cytokines and immune-suppressive cells that could attenuate the inflammation in intestine. Therefore, we believe that CD69 represents a very good target molecule that should be tested for the treatment of IBD.


CD69 is the crucial regulator of intestinal inflammation: a new target molecule for IBD treatment?

Radulovic K, Niess JH - J Immunol Res (2015)

The role of CD69 in mucosal immunity. Activation of intestinal CD4 T cell by antigen recognition, type I interferons (IFN-I), or by presence of intestinal microflora leads to the upregulation of CD69 expression on the cell surface. After binding a ligand, CD69 activates the intracellular pathways that result in decreased production of proinflammatory cytokines (IFN-γ, TNF-α, and IL-21) and chemokines (Ccl-1, Cxcl-10, and Ccl-19) and increased production of regulatory cytokine TGF-β1. If the CD4 T cell establishes a stable expression of CD69, this cell can differentiate into CD69+ regulatory T cell (Treg) or tissue resident memory T cell (TRM). Therefore, upregulation of CD69 leads to the decreased migration of activated CD4 T cells to the intestine and to the increased regulatory responses, which ensures the establishment of oral tolerance and the attenuation of colitis severity.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4352431&req=5

fig3: The role of CD69 in mucosal immunity. Activation of intestinal CD4 T cell by antigen recognition, type I interferons (IFN-I), or by presence of intestinal microflora leads to the upregulation of CD69 expression on the cell surface. After binding a ligand, CD69 activates the intracellular pathways that result in decreased production of proinflammatory cytokines (IFN-γ, TNF-α, and IL-21) and chemokines (Ccl-1, Cxcl-10, and Ccl-19) and increased production of regulatory cytokine TGF-β1. If the CD4 T cell establishes a stable expression of CD69, this cell can differentiate into CD69+ regulatory T cell (Treg) or tissue resident memory T cell (TRM). Therefore, upregulation of CD69 leads to the decreased migration of activated CD4 T cells to the intestine and to the increased regulatory responses, which ensures the establishment of oral tolerance and the attenuation of colitis severity.
Mentions: CD69 has been for decades used as a simple marker of activated leukocytes without knowing any concrete role this receptor could play in the regulation of immune responses. The discovery that CD69 expression depends on the presence of the intestinal microflora opened new insight into the role CD69 has in immunity and inflammation in intestine. Induced by the specific antigen and/or intestinal microflora, CD69 regulates the essential processes such as the migration of lymphocytes, cytokine secretion, and generation of regulatory and memory T cells at the mucosal sites (Figure 3). CD69 directs the immune responses in the intestine toward the oral tolerance and regulatory responses (Figure 3) [48]. In vivo CD69 limited the intestinal inflammation proving to be one of the crucial negative regulators of the immune responses in the gut. The activation of CD69 induces tolerogenic cytokines and immune-suppressive cells that could attenuate the inflammation in intestine. Therefore, we believe that CD69 represents a very good target molecule that should be tested for the treatment of IBD.

Bottom Line: However, recent work has indicated that CD69 plays an essential role for the regulation of inflammatory processes.Particularly, CD69 is highly expressed by lymphocytes at mucosal sites being constantly exposed to the intestinal microflora (one of the nature's most complex and most densely populated microbial habitats) and food antigens, while only a small number of circulating leukocytes express this molecule.In this review we will discuss the role of CD69 in mucosal tissue and consider CD69 as a potential target for the development of novel treatments of intestinal inflammation.

View Article: PubMed Central - PubMed

Affiliation: U1019, Team 7, Institut National de la Santé et de la Recherche Médicale (INSERM), 1 rue du Professeur Calmette, 59019 Lille, France ; Center for Infection and Immunity of Lille, Institut Pasteur de Lille, 1 rue du Professeur Calmette, 59019 Lille, France.

ABSTRACT
CD69 has been identified as an early activation marker of lymphocytes. However, recent work has indicated that CD69 plays an essential role for the regulation of inflammatory processes. Particularly, CD69 is highly expressed by lymphocytes at mucosal sites being constantly exposed to the intestinal microflora (one of the nature's most complex and most densely populated microbial habitats) and food antigens, while only a small number of circulating leukocytes express this molecule. In this review we will discuss the role of CD69 in mucosal tissue and consider CD69 as a potential target for the development of novel treatments of intestinal inflammation.

Show MeSH
Related in: MedlinePlus