Interferon-gamma regulates growth and controls Fcgamma receptor expression and activation in human intestinal mast cells

Research article

Gernot Sellge, Miriam Barkowsky, Sigrid Kramer, Thomas Gebhardt, Leif E Sander, Axel Lorentz and Stephan C Bischoff

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BMC Immunology 2014, 15:27  doi:10.1186/1471-2172-15-27

Published: 5 July 2014

Abstract (provisional)

Background

Development and function of tissue resident mast cells (MCs) is tightly controlled by various cytokines, most of which belong to the typical T helper (Th) 2-type cytokines such as IL-3 and IL-4. The effects of the Th1-type cytokine IFN-gamma on human MCs is less clear.

Results

Here, we analyzed the effects of IFN-gamma on tissue-derived, mature human MCs. We found that INF-gamma decreases proliferation, without affecting apoptosis in human intestinal MCs cultured in the presence of optimal concentrations of stem cell factor (SCF) or SCF and IL-4. However, in the absence of growth factors or at suboptimal concentrations of SCF, INF-gamma promotes survival through inhibition of MC apoptosis. Interestingly, we found that INF-gamma has no effect on FcepsilonRI expression and FcepsilonRI-mediated release of histamine and leukotriene (LT)C4, while it has profound effects on FcgammaR expression and activation. We show that intestinal MCs express FcgammaRI, FcgammaRIIa, and FcgammaRIIc, whereas FcgammaRIIb expression was found in only 40% of the isolates and FcgammaRIII was never detectable. INF-gamma strongly increases FcgammaRI and decreases FcgammaRIIa expression. INF-gamma-naive MCs produce LTC4 but fail to degranulate upon crosslinking of surface-bound monomeric IgG. In contrast, INF-gamma-treated MCs rapidly release granule-stored histamine in addition to de novo-synthesized LTC4.

Conclusion

In summary, we identify INF-gamma as an important regulator of tissue-resident human MCs. IFN-gamma displays a dual function by blocking extensive MC proliferation, while decreasing apoptosis in starving MCs and enhancing FcgammaRI expression and activation. These results emphasize the involvement of mucosal MCs in Th1-mediated disorders.

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