Characterization of the syk-dependent T cell signaling response to an altered peptide

Jeoung Eun Park, Jeffrey A. Rotondo, David L. Cullins, David Brand, Ae-Kyung Yi, John Stuart, Andrew Kang, Linda Myers

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Rheumatoid arthritis is an autoimmune disorder characterized by T cell dysregulation. We have shown that an altered peptide ligand (A9) activates T cells to use an alternate signaling pathway that is dependent on FcRγ and spleen tyrosine kinase, resulting in downregulation of inflammation. In the experiments described in this study, we have attempted to determine the molecular basis of this paradox. Three major Src family kinases found in T cells (Lck, Fyn, and Lyn) were tested for activation following stimulation by A9/I-Aq. Unexpectedly we found they are not required for T cell functions induced by A9/I-Aq, nor are they required for APL stimulation of cytokines. On the other hand, the induction of the second messenger inositol trisphosphate and the mobilization of calcium are clearly triggered by the APL A9/I-Aq stimulation and are required for cytokine production, albeit the cytokines induced are different from those produced after activation of the canonical pathway. DBA/1 mice doubly deficient in IL-4 and IL-10 were used to confirm that these two cytokines are important for the APL-induced attenuation of arthritis. These studies provide a basis for exploring the effectiveness of analog peptides and the inhibitory T cells they induce as therapeutic tools for autoimmune arthritis.

Original languageEnglish (US)
Pages (from-to)4569-4575
Number of pages7
JournalJournal of Immunology
Volume197
Issue number12
DOIs
StatePublished - Dec 15 2016

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T-Lymphocytes
Peptides
Cytokines
Arthritis
Peptide T
Inbred DBA Mouse
src-Family Kinases
Second Messenger Systems
Inositol
Interleukin-4
Interleukin-10
Rheumatoid Arthritis
Down-Regulation
Ligands
Inflammation
Calcium
Therapeutics

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Characterization of the syk-dependent T cell signaling response to an altered peptide. / Park, Jeoung Eun; Rotondo, Jeffrey A.; Cullins, David L.; Brand, David; Yi, Ae-Kyung; Stuart, John; Kang, Andrew; Myers, Linda.

In: Journal of Immunology, Vol. 197, No. 12, 15.12.2016, p. 4569-4575.

Research output: Contribution to journalArticle

Park, Jeoung Eun ; Rotondo, Jeffrey A. ; Cullins, David L. ; Brand, David ; Yi, Ae-Kyung ; Stuart, John ; Kang, Andrew ; Myers, Linda. / Characterization of the syk-dependent T cell signaling response to an altered peptide. In: Journal of Immunology. 2016 ; Vol. 197, No. 12. pp. 4569-4575.
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