Limits...
The role of decay accelerating factor in environmentally induced and idiopathic systemic autoimmune disease.

Toomey CB, Cauvi DM, Pollard KM - Autoimmune Dis (2014)

Bottom Line: Decay accelerating factor (DAF) plays a complex role in the immune system through complement-dependent and -independent regulation of innate and adaptive immunity.In contrast, DAF-mediated T cell activation leads to cytokine expression consistent with T regulatory cells.These observations are used to develop a hypothetical model to explain how DAF expression may impact T cell differentiation via interaction with CD97 leading to T regulatory cells, increased production of IL-10, and immune tolerance.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Duke University School of Medicine, Albert Eye Research Institute, Durham, NC 27710, USA.

ABSTRACT
Decay accelerating factor (DAF) plays a complex role in the immune system through complement-dependent and -independent regulation of innate and adaptive immunity. Over the past five years there has been accumulating evidence for a significant role of DAF in negatively regulating adaptive T-cell responses and autoimmunity in both humans and experimental models. This review discusses the relationship between DAF and the complement system and highlights major advances in our understanding of the biology of DAF in human disease, particularly systemic lupus erythematosus. The role of DAF in regulation of idiopathic and environmentally induced systemic autoimmunity is discussed including studies showing that reduction or absence of DAF is associated with autoimmunity. In contrast, DAF-mediated T cell activation leads to cytokine expression consistent with T regulatory cells. This is supported by studies showing that interaction between DAF and its molecular partner, CD97, modifies expression of autoimmunity promoting cytokines. These observations are used to develop a hypothetical model to explain how DAF expression may impact T cell differentiation via interaction with CD97 leading to T regulatory cells, increased production of IL-10, and immune tolerance.

No MeSH data available.


Related in: MedlinePlus

Overview of the complement system. Stimulated by antigen : antibody complexes, bacterial cell surfaces, and spontaneous hydrolysis, respectively, the classical, lectin, and alternative pathways converge to convert C3 to C3 convertase, an enzyme capable of initiating a cascade that results in cell membrane pore formation and subsequent cell lysis known as the membrane attack complex (MAC). To protect host cells from complement activation four main plasma membrane complement regulatory proteins are expressed, CD59 (membrane inhibitor of reactive lysis (MIRL)), CD35 (type 1 complement receptor (CR1)), CD46 (membrane cofactor protein, (MCP)), and CD55 (decay accelerating factor (DAF)), that interrupt the complement cascade on self-cells. CD59 blocks MAC complex formation, CD35 acts as a cofactor to inactivate C3b and C4b by factor I, and interacts with C3b and C4b to promote immune-complex removal, CD46 acts as a cofactor to inactivate C3b and C4b through factor I and DAF inhibits the cleavage of C3 and C5 by blocking the formation of C3 and C5 convertases and accelerating their decay. MBL: mannose-binding lectin; MASPs: MBL-associated serine proteases; PAMP: pathogen-associated molecular pattern; Fb: factor B.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3921935&req=5

fig1: Overview of the complement system. Stimulated by antigen : antibody complexes, bacterial cell surfaces, and spontaneous hydrolysis, respectively, the classical, lectin, and alternative pathways converge to convert C3 to C3 convertase, an enzyme capable of initiating a cascade that results in cell membrane pore formation and subsequent cell lysis known as the membrane attack complex (MAC). To protect host cells from complement activation four main plasma membrane complement regulatory proteins are expressed, CD59 (membrane inhibitor of reactive lysis (MIRL)), CD35 (type 1 complement receptor (CR1)), CD46 (membrane cofactor protein, (MCP)), and CD55 (decay accelerating factor (DAF)), that interrupt the complement cascade on self-cells. CD59 blocks MAC complex formation, CD35 acts as a cofactor to inactivate C3b and C4b by factor I, and interacts with C3b and C4b to promote immune-complex removal, CD46 acts as a cofactor to inactivate C3b and C4b through factor I and DAF inhibits the cleavage of C3 and C5 by blocking the formation of C3 and C5 convertases and accelerating their decay. MBL: mannose-binding lectin; MASPs: MBL-associated serine proteases; PAMP: pathogen-associated molecular pattern; Fb: factor B.

Mentions: The complement system is among the oldest evolutionary components of the immune system. It was discovered in 1896 as a heat-labile fraction of serum that led to opsonization of bacteria. Biochemical characterization showed that the complement system is composed of over 30 proteins that function to mediate removal of apoptotic cells and eliminate pathogens. Three separate pathways (i.e., classical, alternative, and lectin pathways) converge to convert C3 to C3 convertase, an enzyme capable of initiating a cascade that results in cell membrane pore formation and subsequent cell lysis known as the membrane attack complex (MAC) (Figure 1). To protect host cells from complement activation four plasma membrane complement regulatory proteins are expressed, CD59 (membrane inhibitor of reactive lysis (MIRL)), CD35 (type 1 complement receptor (CR1)), CD46 (membrane cofactor protein (MCP)), and CD55 (decay accelerating factor (DAF)), that interrupt the complement cascade on self-cells. CD59 blocks MAC complex formation [25], CD35 acts as a cofactor to inactivate C3b and C4b by factor I and interacts with C3b and C4b to promote immune-complex removal [9], and CD46 acts as a cofactor to inactivate C3b and C4b through factor I [9]. DAF inhibits the cleavage of C3 and C5 by blocking the formation of C3 and C5 convertases and accelerating their decay [4]. The original premise of the complement system as a member of the innate immune system, however, was redefined three decades ago when it was shown that complement participates in B- and T-cell responses especially the induction and regulation of type I helper (Th1) CD4+ T-cell responses [26].


The role of decay accelerating factor in environmentally induced and idiopathic systemic autoimmune disease.

Toomey CB, Cauvi DM, Pollard KM - Autoimmune Dis (2014)

Overview of the complement system. Stimulated by antigen : antibody complexes, bacterial cell surfaces, and spontaneous hydrolysis, respectively, the classical, lectin, and alternative pathways converge to convert C3 to C3 convertase, an enzyme capable of initiating a cascade that results in cell membrane pore formation and subsequent cell lysis known as the membrane attack complex (MAC). To protect host cells from complement activation four main plasma membrane complement regulatory proteins are expressed, CD59 (membrane inhibitor of reactive lysis (MIRL)), CD35 (type 1 complement receptor (CR1)), CD46 (membrane cofactor protein, (MCP)), and CD55 (decay accelerating factor (DAF)), that interrupt the complement cascade on self-cells. CD59 blocks MAC complex formation, CD35 acts as a cofactor to inactivate C3b and C4b by factor I, and interacts with C3b and C4b to promote immune-complex removal, CD46 acts as a cofactor to inactivate C3b and C4b through factor I and DAF inhibits the cleavage of C3 and C5 by blocking the formation of C3 and C5 convertases and accelerating their decay. MBL: mannose-binding lectin; MASPs: MBL-associated serine proteases; PAMP: pathogen-associated molecular pattern; Fb: factor B.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3921935&req=5

fig1: Overview of the complement system. Stimulated by antigen : antibody complexes, bacterial cell surfaces, and spontaneous hydrolysis, respectively, the classical, lectin, and alternative pathways converge to convert C3 to C3 convertase, an enzyme capable of initiating a cascade that results in cell membrane pore formation and subsequent cell lysis known as the membrane attack complex (MAC). To protect host cells from complement activation four main plasma membrane complement regulatory proteins are expressed, CD59 (membrane inhibitor of reactive lysis (MIRL)), CD35 (type 1 complement receptor (CR1)), CD46 (membrane cofactor protein, (MCP)), and CD55 (decay accelerating factor (DAF)), that interrupt the complement cascade on self-cells. CD59 blocks MAC complex formation, CD35 acts as a cofactor to inactivate C3b and C4b by factor I, and interacts with C3b and C4b to promote immune-complex removal, CD46 acts as a cofactor to inactivate C3b and C4b through factor I and DAF inhibits the cleavage of C3 and C5 by blocking the formation of C3 and C5 convertases and accelerating their decay. MBL: mannose-binding lectin; MASPs: MBL-associated serine proteases; PAMP: pathogen-associated molecular pattern; Fb: factor B.
Mentions: The complement system is among the oldest evolutionary components of the immune system. It was discovered in 1896 as a heat-labile fraction of serum that led to opsonization of bacteria. Biochemical characterization showed that the complement system is composed of over 30 proteins that function to mediate removal of apoptotic cells and eliminate pathogens. Three separate pathways (i.e., classical, alternative, and lectin pathways) converge to convert C3 to C3 convertase, an enzyme capable of initiating a cascade that results in cell membrane pore formation and subsequent cell lysis known as the membrane attack complex (MAC) (Figure 1). To protect host cells from complement activation four plasma membrane complement regulatory proteins are expressed, CD59 (membrane inhibitor of reactive lysis (MIRL)), CD35 (type 1 complement receptor (CR1)), CD46 (membrane cofactor protein (MCP)), and CD55 (decay accelerating factor (DAF)), that interrupt the complement cascade on self-cells. CD59 blocks MAC complex formation [25], CD35 acts as a cofactor to inactivate C3b and C4b by factor I and interacts with C3b and C4b to promote immune-complex removal [9], and CD46 acts as a cofactor to inactivate C3b and C4b through factor I [9]. DAF inhibits the cleavage of C3 and C5 by blocking the formation of C3 and C5 convertases and accelerating their decay [4]. The original premise of the complement system as a member of the innate immune system, however, was redefined three decades ago when it was shown that complement participates in B- and T-cell responses especially the induction and regulation of type I helper (Th1) CD4+ T-cell responses [26].

Bottom Line: Decay accelerating factor (DAF) plays a complex role in the immune system through complement-dependent and -independent regulation of innate and adaptive immunity.In contrast, DAF-mediated T cell activation leads to cytokine expression consistent with T regulatory cells.These observations are used to develop a hypothetical model to explain how DAF expression may impact T cell differentiation via interaction with CD97 leading to T regulatory cells, increased production of IL-10, and immune tolerance.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, Duke University School of Medicine, Albert Eye Research Institute, Durham, NC 27710, USA.

ABSTRACT
Decay accelerating factor (DAF) plays a complex role in the immune system through complement-dependent and -independent regulation of innate and adaptive immunity. Over the past five years there has been accumulating evidence for a significant role of DAF in negatively regulating adaptive T-cell responses and autoimmunity in both humans and experimental models. This review discusses the relationship between DAF and the complement system and highlights major advances in our understanding of the biology of DAF in human disease, particularly systemic lupus erythematosus. The role of DAF in regulation of idiopathic and environmentally induced systemic autoimmunity is discussed including studies showing that reduction or absence of DAF is associated with autoimmunity. In contrast, DAF-mediated T cell activation leads to cytokine expression consistent with T regulatory cells. This is supported by studies showing that interaction between DAF and its molecular partner, CD97, modifies expression of autoimmunity promoting cytokines. These observations are used to develop a hypothetical model to explain how DAF expression may impact T cell differentiation via interaction with CD97 leading to T regulatory cells, increased production of IL-10, and immune tolerance.

No MeSH data available.


Related in: MedlinePlus