The Role of Heat Shock Proteins in Type 1 Diabetes

<div><p>Type 1 diabetes (T1D) is a T-cell mediated autoimmune disease characterized by recognition of pancreatic β-cell proteins as self-antigens, called autoantigens (AAgs), followed by loss of pancreatic β-cells. (Pre-)proinsulin ([P]PI), glutamic acid decarboxylase (GAD), tyrosine pho...

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Main Author: Abu Saleh Md Moin (6189512) (author)
Other Authors: Manjula Nandakumar (1545811) (author), Abdoulaye Diane (14152749) (author), Mohammed Dehbi (309033) (author), Alexandra E. Butler (6189536) (author)
Published: 2021
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author Abu Saleh Md Moin (6189512)
author2 Manjula Nandakumar (1545811)
Abdoulaye Diane (14152749)
Mohammed Dehbi (309033)
Alexandra E. Butler (6189536)
author2_role author
author
author
author
author_facet Abu Saleh Md Moin (6189512)
Manjula Nandakumar (1545811)
Abdoulaye Diane (14152749)
Mohammed Dehbi (309033)
Alexandra E. Butler (6189536)
author_role author
dc.creator.none.fl_str_mv Abu Saleh Md Moin (6189512)
Manjula Nandakumar (1545811)
Abdoulaye Diane (14152749)
Mohammed Dehbi (309033)
Alexandra E. Butler (6189536)
dc.date.none.fl_str_mv 2021-01-14T03:00:00Z
dc.identifier.none.fl_str_mv 10.3389/fimmu.2020.612584
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/The_Role_of_Heat_Shock_Proteins_in_Type_1_Diabetes/25867648
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biomedical and clinical sciences
Clinical sciences
Immunology
type 1 diabetes
heat shock proteins
type 1 diabetes pathogenesis
autoantigens
metabolic stress
antigen specific immunotherapy
dc.title.none.fl_str_mv The Role of Heat Shock Proteins in Type 1 Diabetes
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <div><p>Type 1 diabetes (T1D) is a T-cell mediated autoimmune disease characterized by recognition of pancreatic β-cell proteins as self-antigens, called autoantigens (AAgs), followed by loss of pancreatic β-cells. (Pre-)proinsulin ([P]PI), glutamic acid decarboxylase (GAD), tyrosine phosphatase IA-2, and the zinc transporter ZnT8 are key molecules in T1D pathogenesis and are recognized by autoantibodies detected in routine clinical laboratory assays. However, generation of new autoantigens (neoantigens) from β-cells has also been reported, against which the autoreactive T cells show activity. Heat shock proteins (HSPs) were originally described as “cellular stress responders” for their role as chaperones that regulate the conformation and function of a large number of cellular proteins to protect the body from stress. HSPs participate in key cellular functions under both physiological and stressful conditions, including suppression of protein aggregation, assisting folding and stability of nascent and damaged proteins, translocation of proteins into cellular compartments and targeting irreversibly damaged proteins for degradation. Low HSP expression impacts many pathological conditions associated with diabetes and could play a role in diabetic complications. HSPs have beneficial effects in preventing insulin resistance and hyperglycemia in type 2 diabetes (T2D). HSPs are, however, additionally involved in antigen presentation, presenting immunogenic peptides to class I and class II major histocompatibility molecules; thus, an opportunity exists for HSPs to be employed as modulators of immunologic responses in T1D and other autoimmune disorders. In this review, we discuss the multifaceted roles of HSPs in the pathogenesis of T1D and in autoantigen-specific immune protection against T1D development.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Frontiers in Immunology<br> License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fimmu.2020.612584" target="_blank">https://dx.doi.org/10.3389/fimmu.2020.612584</a></p>
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id Manara2_85a70a683eb07268b8cb52e2874d5c8f
identifier_str_mv 10.3389/fimmu.2020.612584
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/25867648
publishDate 2021
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spelling The Role of Heat Shock Proteins in Type 1 DiabetesAbu Saleh Md Moin (6189512)Manjula Nandakumar (1545811)Abdoulaye Diane (14152749)Mohammed Dehbi (309033)Alexandra E. Butler (6189536)Biomedical and clinical sciencesClinical sciencesImmunologytype 1 diabetesheat shock proteinstype 1 diabetes pathogenesisautoantigensmetabolic stressantigen specific immunotherapy<div><p>Type 1 diabetes (T1D) is a T-cell mediated autoimmune disease characterized by recognition of pancreatic β-cell proteins as self-antigens, called autoantigens (AAgs), followed by loss of pancreatic β-cells. (Pre-)proinsulin ([P]PI), glutamic acid decarboxylase (GAD), tyrosine phosphatase IA-2, and the zinc transporter ZnT8 are key molecules in T1D pathogenesis and are recognized by autoantibodies detected in routine clinical laboratory assays. However, generation of new autoantigens (neoantigens) from β-cells has also been reported, against which the autoreactive T cells show activity. Heat shock proteins (HSPs) were originally described as “cellular stress responders” for their role as chaperones that regulate the conformation and function of a large number of cellular proteins to protect the body from stress. HSPs participate in key cellular functions under both physiological and stressful conditions, including suppression of protein aggregation, assisting folding and stability of nascent and damaged proteins, translocation of proteins into cellular compartments and targeting irreversibly damaged proteins for degradation. Low HSP expression impacts many pathological conditions associated with diabetes and could play a role in diabetic complications. HSPs have beneficial effects in preventing insulin resistance and hyperglycemia in type 2 diabetes (T2D). HSPs are, however, additionally involved in antigen presentation, presenting immunogenic peptides to class I and class II major histocompatibility molecules; thus, an opportunity exists for HSPs to be employed as modulators of immunologic responses in T1D and other autoimmune disorders. In this review, we discuss the multifaceted roles of HSPs in the pathogenesis of T1D and in autoantigen-specific immune protection against T1D development.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Frontiers in Immunology<br> License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fimmu.2020.612584" target="_blank">https://dx.doi.org/10.3389/fimmu.2020.612584</a></p>2021-01-14T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3389/fimmu.2020.612584https://figshare.com/articles/journal_contribution/The_Role_of_Heat_Shock_Proteins_in_Type_1_Diabetes/25867648CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/258676482021-01-14T03:00:00Z
spellingShingle The Role of Heat Shock Proteins in Type 1 Diabetes
Abu Saleh Md Moin (6189512)
Biomedical and clinical sciences
Clinical sciences
Immunology
type 1 diabetes
heat shock proteins
type 1 diabetes pathogenesis
autoantigens
metabolic stress
antigen specific immunotherapy
status_str publishedVersion
title The Role of Heat Shock Proteins in Type 1 Diabetes
title_full The Role of Heat Shock Proteins in Type 1 Diabetes
title_fullStr The Role of Heat Shock Proteins in Type 1 Diabetes
title_full_unstemmed The Role of Heat Shock Proteins in Type 1 Diabetes
title_short The Role of Heat Shock Proteins in Type 1 Diabetes
title_sort The Role of Heat Shock Proteins in Type 1 Diabetes
topic Biomedical and clinical sciences
Clinical sciences
Immunology
type 1 diabetes
heat shock proteins
type 1 diabetes pathogenesis
autoantigens
metabolic stress
antigen specific immunotherapy