OBJECTIVE: T cells from the majority of patients with systemic lupus erythematosus (SLE) express significantly lower levels of T cell receptor zeta chain, a critical signaling molecule. However, TCR/CD3 triggering of SLE T cells shows increased phosphorylation of downstream signaling intermediates and increased [Ca2+]i response, suggesting the presence of alternative signaling mechanisms. We investigated whether Fcepsilon receptor type I gamma chain (FcepsilonRIgamma) could substitute for TCR zeta chain and contribute to T cell signaling in SLE. METHODS: T cells were purified from the peripheral blood of 21 patients with SLE and 5 healthy volunteers. The expression of FcepsilonRIgamma was investigated using immunoblotting, reverse transcriptase-polymerase chain reaction, and flow cytometry methods. Involvement of the FcepsilonRIgamma in T cell signaling was studied by immunoprecipitation and/or immunoblotting after TCR/CD3 stimulation. RESULTS: Western blotting and densitometric analysis showed that the expression of FcepsilonRIgamma in SLE T cells was 4.3-fold higher than in normal T cells (P < 0.001). Flow cytometric analyses of T lymphocyte subsets revealed that the proportions of FcepsilonRIgamma+,CD3+, FcepsilonRIgamma+,CD4+, and FcepsilonRIgamma+, CD8+ cells were significantly greater in SLE patients than in healthy controls (P < 0.001). Immunoprecipitation of SLE T cell lysates with an anti-FcepsilonRIgamma antibody showed that FcepsilonRIgamma associates with the tyrosine kinase Syk and the CD3epsilon chain, suggesting that FcepsilonRIgamma is functionally involved in TCR signaling. CONCLUSION: These results demonstrate that the FcepsilonRIgamma chain is expressed at high levels in a large proportion of SLE T cells. The increased expression of FcepsilonRIgamma chain in SLE T cells may account in part for the aberrant antigen receptor-initiated signaling and contribute to the diverse cellular abnormalities found in this disease.
OBJECTIVE: T cells from the majority of patients with systemic lupus erythematosus (SLE) express significantly lower levels of T cell receptor zeta chain, a critical signaling molecule. However, TCR/CD3 triggering of SLE T cells shows increased phosphorylation of downstream signaling intermediates and increased [Ca2+]i response, suggesting the presence of alternative signaling mechanisms. We investigated whether Fcepsilon receptor type I gamma chain (FcepsilonRIgamma) could substitute for TCR zeta chain and contribute to T cell signaling in SLE. METHODS: T cells were purified from the peripheral blood of 21 patients with SLE and 5 healthy volunteers. The expression of FcepsilonRIgamma was investigated using immunoblotting, reverse transcriptase-polymerase chain reaction, and flow cytometry methods. Involvement of the FcepsilonRIgamma in T cell signaling was studied by immunoprecipitation and/or immunoblotting after TCR/CD3 stimulation. RESULTS: Western blotting and densitometric analysis showed that the expression of FcepsilonRIgamma in SLE T cells was 4.3-fold higher than in normal T cells (P < 0.001). Flow cytometric analyses of T lymphocyte subsets revealed that the proportions of FcepsilonRIgamma+,CD3+, FcepsilonRIgamma+,CD4+, and FcepsilonRIgamma+, CD8+ cells were significantly greater in SLEpatients than in healthy controls (P < 0.001). Immunoprecipitation of SLE T cell lysates with an anti-FcepsilonRIgamma antibody showed that FcepsilonRIgamma associates with the tyrosine kinase Syk and the CD3epsilon chain, suggesting that FcepsilonRIgamma is functionally involved in TCR signaling. CONCLUSION: These results demonstrate that the FcepsilonRIgamma chain is expressed at high levels in a large proportion of SLE T cells. The increased expression of FcepsilonRIgamma chain in SLE T cells may account in part for the aberrant antigen receptor-initiated signaling and contribute to the diverse cellular abnormalities found in this disease.
Authors: Spandan Shah; Andrew W Gibson; Chuanyi Ji; Eric Darrington; James Mobley; Kyoko Kojima; Jeffrey C Edberg; Robert P Kimberly Journal: J Leukoc Biol Date: 2016-09-14 Impact factor: 4.962
Authors: M Martins; A H Williams; M Comeau; M Marion; J T Ziegler; B I Freedman; J T Merrill; S B Glenn; J A Kelly; K M Sivils; J A James; J M Guthridge; M E Alarcón-Riquelme; S-C Bae; J-H Kim; D Kim; J-M Anaya; S A Boackle; L A Criswell; R P Kimberly; G S Alarcón; E E Brown; L M Vilá; M A Petri; R Ramsey-Goldman; T B Niewold; B P Tsao; G S Gilkeson; D L Kamen; C O Jacob; A M Stevens; P M Gaffney; J B Harley; C D Langefeld; C Fesel Journal: Genes Immun Date: 2015-01-08 Impact factor: 2.676