| Fibrosis is a reaction of a fibroblast to injury. Upon activation, the fibroblast becomes a myofibroblast, |
| which produces (intracellular) myosin and starts secreting matrix proteins, particularly collagens [33]. |
| This local fibrotic damage control program is often accompanied by an inflammatory reaction [34]. |
| The inflammation generates an influx of external “damage controllers,” including granulocytes, monocytes, lymphocytes, |
| and the recently recognized monocyte-related fibrocyte [35, 36]. Depending on the nature and the time course of the damage |
| the cellular composition of the infiltrate will vary markedly, which results in a broad spectrum of tissue changes. |
| Macrophages are assumed to play a crucial role in the regulation of inflammation and fibrosis [37]. |
| In IgG4-related fibrosis, the contribution of neutrophils is typically small. |
| In the pancreas, the cell most prominently involved in fibrotic reactions is often referred to as “spindle cell,” |
| which is not a well-defined (myo-) fibroblast cell type. In 1998, a fibroblast-related cell with all characteristics of |
| the hepatic stellate cell was identified in the pancreas [38]. The stellate cell is also known as “lipocyte,” |
| because of the presence of many lipid-containing vesicles that show a typical autofluorescence caused |
| by the presence of vitamin A [39]. The presence of these lipid vesicles results in a characteristic low buoyant density, which can |
| be used to isolate stellate cells. Hepatic stellate cells have been found to be closely associated with plasma cells in hepatic fibrosis |
| [40]. Upon activation, the stellate cell releases much of its lipid vesicles, which makes it more difficult to distinguish it |
| from other myofibroblast-related cells. For a recent review on the pancreatic stellate cell, see [41]. |
| In IgG4-related fibrosis, the characteristic pattern is described as “storiform,” a whirling pattern. |
| This pattern presumably reflects the interaction of clusters of proliferating myofibroblasts [42]. |
| One of the functions of myofibroblasts is to contract during a wound |
| healing process. Such a contraction in the absence of a wound to heal may result in a whirling pattern. Plasma cells |
| (of which typically more than 40% are IgG4 producing) are found within this fibrotic network, suggesting that this could be |
| a niche for the IgG4 plasma cells in IRD. |
