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Complement proteins enriched in dextran-based microparticle

ABSTRACT: Autoimmunity affects ~10% of the global population. Current therapies suppress protective immunity and are non-curative. Antigen-specific therapies can selectively suppress autoreactive cells, preserving protective immunity. B cell dysregulation, a major driver of autoimmunity, remains largely untargeted. We hypothesized that targeting B cells with antigen-loaded microparticles enhances therapeutic efficacy. Here, we demonstrate that antigen-loaded acetalated dextran microparticles (AMP) surface-associate with B cells and enhance IL-10 secretion and MHCII expression, promoting tolerogenic antigen presentation. Leveraging this property, we developed a therapy using myelin oligodendrocyte (MOG35-55) peptide-loaded AMPs associated with B cells (MOG-AMP-B). Administering MOG-AMP-Bs in a late therapeutic model of multiple sclerosis resulted in unprecedented recovery, reducing central nervous system (CNS) inflammation, downregulating activated dendritic cells and macrophages and increasing regulatory T- and B cells. MOG-AMP-Bs did not reduce the ability of animals to respond to a viral infection, representing a highly effective antigen-specific therapy for restoring immune balance in autoimmunity. This study includes proteomics on the AMP particles after serum exposure, identifying complement proteins enriched on its protein corona.

INSTRUMENT(S):

ORGANISM(S): Bos Taurus (bovine)

SUBMITTER: Scott Lyons

LAB HEAD: Kristy Ainslie

PROVIDER: PXD077329 | Pride | 2026-05-19

REPOSITORIES: Pride

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			Action	DRS
	20241017_PHCOQEHF_PC1357-Ainslie_1.raw	Raw
	20241017_PHCOQEHF_PC1357-Ainslie_2.raw	Raw
	20241017_PHCOQEHF_PC1357-Ainslie_3.raw	Raw
	20241017_PHCOQEHF_PC1357-Ainslie_4.raw	Raw
	20241017_PHCOQEHF_PC1357-Ainslie_5.raw	Raw

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Project description:This is system 1, the model with linear antigen uptake by pAPCs, described in the article: Self-tolerance and Autoimmunity in a Regulatory T Cell Model. Alexander HK, Wahl LM. Bull Math Biol. 2010 Mar 2. PMID:20195912, doi:10.1007/s11538-010-9519-2; Abstract: The class of immunosuppressive lymphocytes known as regulatory T cells (Tregs) has been identified as a key component in preventing autoimmune diseases. Although Tregs have been incorporated previously in mathematical models of autoimmunity, we take a novel approach which emphasizes the importance of professional antigen presenting cells (pAPCs). We examine three possible mechanisms of Treg action (each in isolation) through ordinary differential equation (ODE) models. The immune response against a particular autoantigen is suppressed both by Tregs specific for that antigen and by Tregs of arbitrary specificities, through their action on either maturing or already mature pAPCs or on autoreactive effector T cells. In this deterministic approach, we find that qualitative long-term behaviour is predicted by the basic reproductive ratio R (0) for each system. When R (0) 1, this equilibrium loses its stability and a stable non-trivial equilibrium appears. We interpret the absence of self-damaging populations at the trivial equilibrium to imply a state of self-tolerance, and their presence at the non-trivial equilibrium to imply a state of chronic autoimmunity. Irrespective of mechanism, our model predicts that Tregs specific for the autoantigen in question play no role in the system's qualitative long-term behaviour, but have quantitative effects that could potentially reduce an autoimmune response to sub-clinical levels. Our results also suggest an important role for Tregs of arbitrary specificities in modulating the qualitative outcome. A stochastic treatment of the same model demonstrates that the probability of developing a chronic autoimmune response increases with the initial exposure to self antigen or autoreactive effector T cells. The three different mechanisms we consider, while leading to a number of similar predictions, also exhibit key differences in both transient dynamics (ODE approach) and the probability of chronic autoimmunity (stochastic approach). Originally created by libAntimony v1.4 (using libSBML 3.4.1)

Project description:This is system 2, the model with Michelis Menten type antigen uptake by pAPCs, described in the article: Self-tolerance and Autoimmunity in a Regulatory T Cell Model. Alexander HK, Wahl LM. Bull Math Biol. 2010 Mar 2. PMID: 20195912 , doi: 10.1007/s11538-010-9519-2 ; Abstract: The class of immunosuppressive lymphocytes known as regulatory T cells (Tregs) has been identified as a key component in preventing autoimmune diseases. Although Tregs have been incorporated previously in mathematical models of autoimmunity, we take a novel approach which emphasizes the importance of professional antigen presenting cells (pAPCs). We examine three possible mechanisms of Treg action (each in isolation) through ordinary differential equation (ODE) models. The immune response against a particular autoantigen is suppressed both by Tregs specific for that antigen and by Tregs of arbitrary specificities, through their action on either maturing or already mature pAPCs or on autoreactive effector T cells. In this deterministic approach, we find that qualitative long-term behaviour is predicted by the basic reproductive ratio R (0) for each system. When R (0) 1, this equilibrium loses its stability and a stable non-trivial equilibrium appears. We interpret the absence of self-damaging populations at the trivial equilibrium to imply a state of self-tolerance, and their presence at the non-trivial equilibrium to imply a state of chronic autoimmunity. Irrespective of mechanism, our model predicts that Tregs specific for the autoantigen in question play no role in the system's qualitative long-term behaviour, but have quantitative effects that could potentially reduce an autoimmune response to sub-clinical levels. Our results also suggest an important role for Tregs of arbitrary specificities in modulating the qualitative outcome. A stochastic treatment of the same model demonstrates that the probability of developing a chronic autoimmune response increases with the initial exposure to self antigen or autoreactive effector T cells. The three different mechanisms we consider, while leading to a number of similar predictions, also exhibit key differences in both transient dynamics (ODE approach) and the probability of chronic autoimmunity (stochastic approach). Originally created by libAntimony v1.4 (using libSBML 3.4.1)

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Complement proteins enriched in dextran-based microparticle

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