ORCID Profile
0000-0002-9480-6843
Current Organisations
University College London
,
Moorfields Eye Hospital NHS Foundation Trust
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Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2015
Publisher: Informa UK Limited
Date: 19-11-2019
Publisher: The American Association of Immunologists
Date: 05-2017
Publisher: Elsevier BV
Date: 04-2015
DOI: 10.1016/J.JAUT.2014.12.004
Abstract: Annexin-A1 (Anx-A1) is an endogenous anti-inflammatory molecule and while described as a repressor of innate immune responses, the role of Anx-A1 in adaptive immunity, and in particular in T helper (Th) cell responses, remains controversial. We have used a T-cell mediated mouse model of retinal autoimmune disease to unravel the role of Anx-A1 in the development of autoreactive Th cell responses and pathology. RBP1-20-immunized C57BL/6 Anx-A1(-/-) mice exhibit significantly enhanced retinal inflammation and pathology as a result of an uncontrolled proliferation and activation of Th17 cells. This is associated with a limited capacity to induce SOCS3, resulting in un-restricted phosphorylation of STAT3. RBP1-20-specific CD4(+) cells from immunized Anx-A1(-/-) animals generated high levels of Th17 cells-associated cytokines. Following disease induction, daily systemic administration of human recombinant Anx-A1 (hrAnx-A1), during the afferent phase of disease, restrained autoreactive CD4(+) cell proliferation, reduced expression of pro-inflammatory cytokines IL-17, IFN-γ and IL-6 and attenuated autoimmune retinal inflammatory disease. Furthermore, in man, Anx-A1 serum levels when measured in active uveitis patient sera were low and associated with the detection of IgM and IgG anti-Anx-A1 antibodies when compared to healthy in iduals. This data supports Anx-A1 as an early and critical regulator of Th17 cell driven autoimmune diseases such as uveitis.
Publisher: Wiley
Date: 06-10-2019
DOI: 10.1111/IMCB.12288
Abstract: The genomes of classical inbred mouse strains include genes derived from all three major subspecies of the house mouse, Mus musculus. We recently posited that genetic ersity in the immunoglobulin heavy chain (IGH) gene loci of C57BL/6 and BALB/c mice reflects differences in subspecies origin. To investigate this hypothesis, we conducted high-throughput sequencing of IGH gene rearrangements to document IGH variable (IGHV), joining (IGHJ) and ersity (IGHD) genes in four inbred wild-derived mouse strains (CAST/EiJ, LEWES/EiJ, MSM/MsJ and PWD/PhJ) and a single disease model strain (NOD/ShiLtJ), collectively representing genetic backgrounds of several major mouse subspecies. A total of 341 germline IGHV sequences were inferred in the wild-derived strains, including 247 not curated in the international ImMunoGeneTics information system. By contrast, 83/84 inferred NOD IGHV genes had previously been observed in C57BL/6 mice. Variability among the strains examined was observed for only a single IGHJ gene, involving a description of a novel allele. By contrast, unexpected variation was found in the IGHD gene loci, with four previously unreported IGHD gene sequences being documented. Very few IGHV sequences of C57BL/6 and BALB/c mice were shared with strains representing major subspecies, suggesting that their IGH loci may be complex mosaics of genes of disparate origins. This suggests a similar level of ersity is likely present in the IGH loci of other classical inbred strains. This must now be documented if we are to properly understand interstrain variation in models of antibody-mediated disease.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Richard Lee.