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Volume 8, Issue 3 (Suppl)
J Clin Cell Immunol, an open access journal
ISSN: 2155-9899
Euro Immunology 2017
June 29-July 01, 2017
June 29-July 01, 2017 Madrid, Spain
8
th
European
Immunology Conference
J Clin Cell Immunol 2017, 8:3(Suppl)
DOI: 10.4172/2155-9899-C1-037
Investigation of a T cell subset that constitutively signals via STAT1 activation and is unresponsive to
JAK1 inhibition: Apotential mechanism of T cell subset autoimmune activation
Christopher Gaunt
1, 2
1
University of Cambridge, UK
2
GlaxoSmithKline, UK
Introduction:
JAK-STAT (Janus kinase-signal transducer and activator of transcription) is a conserved cell signalling pathway
responsible for transduction of signal induced by receptors for a diverse range of interferons, cytokines and growth factors.
Polymorphisms of JAKs and STATs are functionally and clinically relevant to a variety of human diseases, particularly cancer and
immune-related, but also common multigenic diseases.
Statement of the Problem:
A population of CD4+ T cells demonstrating constitutive STAT1 phosphorylation were identified both in
systemic lupus erythmatosus (SLE) patients and healthy volunteers. STAT1 phosphorylation in these cells is both independent of IL-6
stimulation and resistant to JAK1 inhibition. These cells may represent a novel paradigm of JAK-independent STAT activation, giving
rise to a pathogenic population that is aberrantly regulated during activation in autoimmune disorders. The aim of this preliminary
research was to confirm the existence of this population and begin characterisation of an extracellular phenotype in the hope of
identifying population-specific markers.
Methods:
The expression of various surface (CD3, CD4, CD25, CD127, CD45RA, CD197, CXCR3 and CCR6) and intracellular
(pSTAT1, pSTAT5, FOXP3) markers in whole blood or isolated lymphocytes from 106 healthy volunteers were analysed by flow
cytometry.
Results:
The constitutively signalling population was demonstrated to persist for up to 48 h in un-stimulated samples and in the
presence of a selective JAK1 inhibitor. The population demonstrated a CD25 low/intermediate and CD127+ phenotype, with FOXP3
expression in some cells. The population was shown to be CD45RA-, indicative of a T-memory cell phenotype. Chemokine receptor
analysis demonstrated the population to be CXCR3- and CCR6+, indicative of a Th17-like phenotype.
Conclusion:
The constitutive STAT1 signalling population may represent a terminally activated group of CD4+ cells that can no
longer regulate STAT activation through potential loss of regulatory mechanisms (SOCS) or constitutive kinase activation, that may
be driving autoimmune disease.
cmg65@cam.ac.uk