Induction of intestinal lymphoid tissue: the role of cryptopatches

The intestinal immune system includes several organized structures, such as Peyer's patches, isolated lymphoid follicles (ILFs), cryptopatches (CPs) as well as mesenteric lymph nodes (MLNs) that constitute an extensive network with other nonorganized parts, such as intraepithelial and lamina propria lymphocytes. CPs are small clusters of lymphoid cells with an immature lymphocyte phenotype and dendritic cells. Initial observations in transfer experiments suggested that the immature lymphocytes are T cell precursors and CPs are a potential site of extrathymic intraepithelial lymphocyte (IEL) differentiation. This feature has recently been challenged particularly by the observation that CP cells express the orphan receptor RORgammat and are phenotypically indistinguishable from lymphoid tissue-inducer (LTi) cells, suggesting that CP cells are the adult counterpart of fetal LTi cells. In addition, the chemokine receptor CCR6 is specifically expressed by precursor cells within CPs and its deletion inhibits the development of ILFs. Therefore, it is likely that ILFs derive from CPs under the control of CCR6 under inflammatory conditions and might constitute a valuable target for anti-inflammatory therapies.