Computational model to analyze and characterize the functional mutations of NOD2 protein causing inflammatory disorder – Blau syndrome

Advances in Protein Chemistry and Structural Biology - Inflammatory Disorders - Part B ◽

10.1016/bs.apcsb.2019.11.005 ◽

2020 ◽

pp. 379-408 ◽

Cited By ~ 4

Author(s):

D. Thirumal Kumar ◽

S. Udhaya Kumar ◽

Ahmed Shaikh Nishaat Laeeque ◽

Shivalkar Apurva Abhay ◽

R. Bithia ◽

...

Keyword(s):

Computational Model ◽

Inflammatory Disorder ◽

Blau Syndrome

Download Full-text

Detection ofMycobacterium avium ss. Paratuberculosisin Blau Syndrome Tissues

Autoimmune Diseases ◽

10.4061/2010/127692 ◽

2010 ◽

Vol 2010 ◽

pp. 1-5 ◽

Cited By ~ 8

Author(s):

C. Thomas Dow ◽

Jay L. E. Ellingson

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Clinical Findings ◽

Innate Immune ◽

Inflammatory Disorder ◽

Blau Syndrome ◽

Environmental Aspects ◽

Chromosome 16 ◽

Dna Evidence ◽

Systemic Inflammatory Disease

Background and Aim of the Work. Blau syndrome is an inherited granulomatous inflammatory disorder with clinical findings of uveitis, arthritis, and dermatitis. Although rare, Blau syndrome shares features with the more common diseases sarcoidosis and Crohn's disease. The clinical findings of Blau syndrome are indistinguishable from juvenile sarcoidosis; the mutations of Blau syndrome are on the same gene of chromosome 16 (CARD15) that confers susceptibility to Crohn's disease. The product of this gene is part of the innate immune system.Mycobacterium avium ss. paratuberculosis(MAP) is the putative cause of Crohn's disease and has been implicated as a causative agent of sarcoidosis.Methods. Archival tissues of individuals with Blau syndrome were tested for the presence of MAP.Results. DNA evidence of MAP was detected in all of the tissues.Conclusions. This article finds that MAP is present in Blau syndrome tissue and postulates that it has a causal role. The presence of MAP in Blau syndrome—an autosomal dominant, systemic inflammatory disease—connects genetic and environmental aspects of “autoimmune” disease.

Download Full-text

T cell-intrinsic role for Nod2 in protection against Th17-mediated uveitis

Nature Communications ◽

10.1038/s41467-020-18961-0 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Ruth J. Napier ◽

Ellen J. Lee ◽

Michael P. Davey ◽

Emily E. Vance ◽

João M. Furtado ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Nucleotide Binding ◽

Inflammatory Disorder ◽

Blau Syndrome ◽

Cellular Mechanisms ◽

Independent Mechanism ◽

Intrinsic Function ◽

Oligomerization Domain

Abstract Mutations in nucleotide-binding oligomerization domain-containing protein 2 (NOD2) cause Blau syndrome, an inflammatory disorder characterized by uveitis. The antimicrobial functions of Nod2 are well-established, yet the cellular mechanisms by which dysregulated Nod2 causes uveitis remain unknown. Here, we report a non-conventional, T cell-intrinsic function for Nod2 in suppression of Th17 immunity and experimental uveitis. Reconstitution of lymphopenic hosts with Nod2−/− CD4+ T cells or retina-specific autoreactive CD4+ T cells lacking Nod2 reveals a T cell-autonomous, Rip2-independent mechanism for Nod2 in uveitis. In naive animals, Nod2 operates downstream of TCR ligation to suppress activation of memory CD4+ T cells that associate with an autoreactive-like profile involving IL-17 and Ccr7. Interestingly, CD4+ T cells from two Blau syndrome patients show elevated IL-17 and increased CCR7. Our data define Nod2 as a T cell-intrinsic rheostat of Th17 immunity, and open new avenues for T cell-based therapies for Nod2-associated disorders such as Blau syndrome.

Download Full-text