Interferon-γ regulates growth and controls Fcγ receptor expression and activation in human intestinal mast cells

BMC Immunology

Stephan C Bischoff²  Axel Lorentz²  Leif E Sander¹  Thomas Gebhardt⁴  Sigrid Kramer²  Miriam Barkowsky⁵  Gernot Sellge³ 

[1] Departmant of Internal Medicine/Infectious Diseases and Respiratory Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany;Department of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany;Department of Internal Medicine III, University Hospital Aachen, RWTH University, Aachen, Germany;Department of Microbiology and Immunology, The University of Melbourne, Melbourne, Australia;Department of Obstetrics and Gynecology, Cologne Municipal Health Care, Cologne, Germany

关键词: Fcγ receptors;    Interferon-γ;    Intestine;    Mast cells;    Human;   

Others  :  823161
DOI  :  10.1186/1471-2172-15-27

 received in 2014-03-13, accepted in 2014-06-20,  发布年份 2014

【 摘 要 】

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-γ on human MCs is less clear.

Results

Here, we analyzed the effects of IFN-γ on tissue-derived, mature human MCs. We found that INF-γ 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-γ promotes survival through inhibition of MC apoptosis. Interestingly, we found that INF-γ has no effect on FcϵRI expression and FcϵRI-mediated release of histamine and leukotriene (LT)C_4, while it has profound effects on FcγR expression and activation. We show that intestinal MCs express FcγRI, FcγRIIa, and FcγRIIc, whereas FcγRIIb expression was found in only 40% of the isolates and FcγRIII was never detectable. INF-γ strongly increases FcγRI and decreases FcγRIIa expression. INF-γ-naïve MCs produce LTC₄ but fail to degranulate upon crosslinking of surface-bound monomeric IgG. In contrast, INF-γ-treated MCs rapidly release granule-stored histamine in addition to de novo-synthesized LTC₄.

Conclusion

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

【 授权许可】

   
2014 Sellge et al.; licensee BioMed Central Ltd.

【 图 表 】

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