Contribution of Mast Cell-Derived Interleukin-1 beta to Uric Acid Crystal-Induced Acute Arthritis in Mice
ARTHRITIS & RHEUMATOLOGY
2014; 66 (10): 2881-2891
Reply: To PMID 23518141.
journal of allergy and clinical immunology
2013; 132 (6): 1458-1459
Human mast cells drive memory CD4(+) T cells toward an inflammatory IL-22(+) phenotype
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
2013; 131 (5): 1400-U240
Cell-cell cooperation at the T helper cell/mast cell immunological synapse
2009; 114 (24): 4979-4988
Mast cells are key components of the skin microenvironment in psoriasis, yet their functional role in this T-cell-mediated inflammatory disorder remains to be elucidated.To define the impact of T-cell/mast-cell cognate interactions on the cytokines produced by TH cells.We used human primary mast cells and effector/memory CD4(+) T cells for in vitro coculture experiments, and we analyzed TH cells responses by using cytometry. CD4(+) T-cell/mast-cell conjugates in skin lesions from patients with psoriasis were analyzed by using 3-color immunohistochemistry and confocal microscopy.We show that IFN-γ-primed human mast cells formed productive immunologic synapses with antigen-experienced CD4(+) T cells. These interactions promoted the generation of TH22 and IL-22/IFN-γ-producing TH cells from the circulating memory CD4(+) T-cell pool via a TNF-α/IL-6-dependent mechanism. An analysis of human psoriatic skin biopsies showed a rich infiltrate of IL-22(+)CD4(+) T cells frequently found in contact with mast cells. Moreover, most of these mast-cell-conjugated lymphocytes coexpressed IFN-γ, suggesting that IL-22(+)IFN-γ(+) CD4(+) T cells are generated in vivo on interaction with mast cells.Our findings identify human mast cells as functional partners of TH cells, shaping their responses toward IL-22 production.
View details for DOI 10.1016/j.jaci.2013.01.029
View details for Web of Science ID 000318912200018
View details for PubMedID 23518141
It has been suggested that mast cells might serve, under certain circumstances, as antigen-presenting cells (APCs) for T cells. However, whether cognate interactions between mast cells and class II-restricted CD4(+) T cells actually occur is still an open question. We addressed this question by using peritoneal cell-derived mast cells (PCMCs) and freshly isolated peritoneal mast cells as APC models. Our results show that in vitro treatment of PCMCs with interferon-gamma and interleukin-4 induced surface expression of mature major histocompatibility complex class II molecules and CD86. When interferon-gamma/interleukin-4-primed PCMCs were used as APCs for CD4(+) T cells, they induced activation of effector T cells but not of their naive counterparts as evidenced by CD69 up-regulation, proliferation, and cytokine production. Confocal laser scanning microscopy showed that CD4(+) T cells formed immunological synapses and polarized their secretory machinery toward both antigen-loaded PCMCs and freshly isolated peritoneal mast cells. Finally, on cognate interaction with CD4(+) T cells, mast cells lowered their threshold of activation via FcepsilonRI. Our results show that mast cells can establish cognate interactions with class II-restricted helper T cells, implying that they can actually serve as resident APCs in inflamed tissues.
View details for DOI 10.1182/blood-2009-02-202648
View details for Web of Science ID 000272403000014
View details for PubMedID 19805617