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Mast Cells are Important Modifiers of Autoimmune Disease: With so Much Evidence, Why is There Still Controversy?

Brown MA, Hatfield JK - Front Immunol (2012)

Bottom Line: Similar to their role as first responders in infection settings, mast cells likely orchestrate early recruitment of immune cells, including neutrophils, to the sites of autoimmune destruction.This co-localization promotes cellular crosstalk and activation and results in the amplification of the local inflammatory response thereby promoting and sustaining tissue damage.However, these potent immune cells are undoubtedly major contributors to autoimmunity and should be considered as important targets for therapeutic disease intervention.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Northwestern University Feinberg School of Medicine Chicago, IL, USA.

ABSTRACT
There is abundant evidence that mast cells are active participants in events that mediate tissue damage in autoimmune disease. Disease-associated increases in mast cell numbers accompanied by mast cell degranulation and elaboration of numerous mast cell mediators at sites of inflammation are commonly observed in many human autoimmune diseases including multiple sclerosis, rheumatoid arthritis, and bullous pemphigoid. In animal models, treatment with mast cell stabilizing drugs or mast cell ablation can result in diminished disease. A variety of receptors including those engaged by antibody, complement, pathogens, and intrinsic danger signals are implicated in mast cell activation in disease. Similar to their role as first responders in infection settings, mast cells likely orchestrate early recruitment of immune cells, including neutrophils, to the sites of autoimmune destruction. This co-localization promotes cellular crosstalk and activation and results in the amplification of the local inflammatory response thereby promoting and sustaining tissue damage. Despite the evidence, there is still a debate regarding the relative role of mast cells in these processes. However, by definition, mast cells can only act as accessory cells to the self-reactive T and/or antibody driven autoimmune responses. Thus, when evaluating mast cell involvement using existing and somewhat imperfect animal models of disease, their importance is sometimes obscured. However, these potent immune cells are undoubtedly major contributors to autoimmunity and should be considered as important targets for therapeutic disease intervention.

No MeSH data available.


Related in: MedlinePlus

Mast cell activation and response in autoimmunity. (A) Mast cells express a variety of activating receptors that may play a role in modifying autoimmune disease. These include IgG receptors FcγR1, FcγRIIB, and FcγRIII; the high affinity IgE receptor, FcεR1; complement receptors C3R and C5aR; TLRs and NLRs that sense pathogen and intrinsic danger signals; as well as LTβR and ICAM-1 which can engage with LTβR-ligand and LFA-1, respectively, on T cells. (B) Mast cells, through expression of cell surface interaction molecules or mast cell-derived mediators, engage in critical cross-talk with many cells of the innate and adaptive immune system. Demonstrated effects of mast cells include elicitation of dendritic cell (DC) and neutrophil (PMN) maturation and recruitment. Mast cells interact directly with B cells to affect activation, proliferation and differentiation. Mast cells can affect the development of CD4+ T helper cells, can act as antigen presenting cells and express mediators and cell surface molecules that co-stimulate and activate T cells. Mast cells can also inhibit or support T regulatory cell function, depending on the setting.
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Figure 2: Mast cell activation and response in autoimmunity. (A) Mast cells express a variety of activating receptors that may play a role in modifying autoimmune disease. These include IgG receptors FcγR1, FcγRIIB, and FcγRIII; the high affinity IgE receptor, FcεR1; complement receptors C3R and C5aR; TLRs and NLRs that sense pathogen and intrinsic danger signals; as well as LTβR and ICAM-1 which can engage with LTβR-ligand and LFA-1, respectively, on T cells. (B) Mast cells, through expression of cell surface interaction molecules or mast cell-derived mediators, engage in critical cross-talk with many cells of the innate and adaptive immune system. Demonstrated effects of mast cells include elicitation of dendritic cell (DC) and neutrophil (PMN) maturation and recruitment. Mast cells interact directly with B cells to affect activation, proliferation and differentiation. Mast cells can affect the development of CD4+ T helper cells, can act as antigen presenting cells and express mediators and cell surface molecules that co-stimulate and activate T cells. Mast cells can also inhibit or support T regulatory cell function, depending on the setting.

Mentions: There are a multitude of receptors expressed on mast cells that are candidates for involvement in autoimmune modulation (Figure 2). As discussed below, many of these receptors and their ligands have been implicated in autoimmune disease, but whether they are acting to activate mast cells in the context of disease is still in question.


Mast Cells are Important Modifiers of Autoimmune Disease: With so Much Evidence, Why is There Still Controversy?

Brown MA, Hatfield JK - Front Immunol (2012)

Mast cell activation and response in autoimmunity. (A) Mast cells express a variety of activating receptors that may play a role in modifying autoimmune disease. These include IgG receptors FcγR1, FcγRIIB, and FcγRIII; the high affinity IgE receptor, FcεR1; complement receptors C3R and C5aR; TLRs and NLRs that sense pathogen and intrinsic danger signals; as well as LTβR and ICAM-1 which can engage with LTβR-ligand and LFA-1, respectively, on T cells. (B) Mast cells, through expression of cell surface interaction molecules or mast cell-derived mediators, engage in critical cross-talk with many cells of the innate and adaptive immune system. Demonstrated effects of mast cells include elicitation of dendritic cell (DC) and neutrophil (PMN) maturation and recruitment. Mast cells interact directly with B cells to affect activation, proliferation and differentiation. Mast cells can affect the development of CD4+ T helper cells, can act as antigen presenting cells and express mediators and cell surface molecules that co-stimulate and activate T cells. Mast cells can also inhibit or support T regulatory cell function, depending on the setting.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3369183&req=5

Figure 2: Mast cell activation and response in autoimmunity. (A) Mast cells express a variety of activating receptors that may play a role in modifying autoimmune disease. These include IgG receptors FcγR1, FcγRIIB, and FcγRIII; the high affinity IgE receptor, FcεR1; complement receptors C3R and C5aR; TLRs and NLRs that sense pathogen and intrinsic danger signals; as well as LTβR and ICAM-1 which can engage with LTβR-ligand and LFA-1, respectively, on T cells. (B) Mast cells, through expression of cell surface interaction molecules or mast cell-derived mediators, engage in critical cross-talk with many cells of the innate and adaptive immune system. Demonstrated effects of mast cells include elicitation of dendritic cell (DC) and neutrophil (PMN) maturation and recruitment. Mast cells interact directly with B cells to affect activation, proliferation and differentiation. Mast cells can affect the development of CD4+ T helper cells, can act as antigen presenting cells and express mediators and cell surface molecules that co-stimulate and activate T cells. Mast cells can also inhibit or support T regulatory cell function, depending on the setting.
Mentions: There are a multitude of receptors expressed on mast cells that are candidates for involvement in autoimmune modulation (Figure 2). As discussed below, many of these receptors and their ligands have been implicated in autoimmune disease, but whether they are acting to activate mast cells in the context of disease is still in question.

Bottom Line: Similar to their role as first responders in infection settings, mast cells likely orchestrate early recruitment of immune cells, including neutrophils, to the sites of autoimmune destruction.This co-localization promotes cellular crosstalk and activation and results in the amplification of the local inflammatory response thereby promoting and sustaining tissue damage.However, these potent immune cells are undoubtedly major contributors to autoimmunity and should be considered as important targets for therapeutic disease intervention.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, Northwestern University Feinberg School of Medicine Chicago, IL, USA.

ABSTRACT
There is abundant evidence that mast cells are active participants in events that mediate tissue damage in autoimmune disease. Disease-associated increases in mast cell numbers accompanied by mast cell degranulation and elaboration of numerous mast cell mediators at sites of inflammation are commonly observed in many human autoimmune diseases including multiple sclerosis, rheumatoid arthritis, and bullous pemphigoid. In animal models, treatment with mast cell stabilizing drugs or mast cell ablation can result in diminished disease. A variety of receptors including those engaged by antibody, complement, pathogens, and intrinsic danger signals are implicated in mast cell activation in disease. Similar to their role as first responders in infection settings, mast cells likely orchestrate early recruitment of immune cells, including neutrophils, to the sites of autoimmune destruction. This co-localization promotes cellular crosstalk and activation and results in the amplification of the local inflammatory response thereby promoting and sustaining tissue damage. Despite the evidence, there is still a debate regarding the relative role of mast cells in these processes. However, by definition, mast cells can only act as accessory cells to the self-reactive T and/or antibody driven autoimmune responses. Thus, when evaluating mast cell involvement using existing and somewhat imperfect animal models of disease, their importance is sometimes obscured. However, these potent immune cells are undoubtedly major contributors to autoimmunity and should be considered as important targets for therapeutic disease intervention.

No MeSH data available.


Related in: MedlinePlus