Beyond Th2, more than ILC2

In Allergology International (AI) Vol. 66, Issue 3, we offer a set of review articles entitled “Beyond Th2, more than ILC2” as well as original articles and letters to the editor. We believe that this issue will be of great help in understanding how several newly emerging cells shape type 2 inflammation. We can say that the discovery of IgE by Ishizaka in 1966 opened the door to molecular research in allergy. The explosive development of molecular biology and immunology, beginning in the 1970s, has expanded our understanding of the underlying mechanisms of allergic inflammation. The biggest breakthrough in this field would be the Th1/Th2 paradigm proposed by Mosmann and Coffman in 1986.1 This theory proposed that there exist Th1 cells and Th2 cells in helper T cells and that these cells show different cytokine production profiles and play different pathophysiological roles. Then based on this theory, it became widely accepted in the 1990s that Th2 cells play a crucial role in the pathogenesis of allergic diseases. Moreover, this knowledge has now led to the development of novel agents against allergic diseases targeting signature type 2 cytokinesdIL-4, IL-5, and IL-13dproduced by Th2 cells. The development of immunology after 2000 has furthermore shaped the details of type 2 inflammation, originally thought to be caused by Th2 cells. The discovery of innate lymphoid cells (ILCs) is one of the most important successes, and right now ILC2 is receiving great attention as the cells that initiate type 2 inflammation.2 However, ILC2s are not the only newly emerging cells that have appeared to be involved in type 2 inflammation. This review series highlights several such cells under investigation by expert researchers. Prof. Nakayama's group first introduces memory-type pathogenic Th2 (Tpath2) cells.3 Tpath2 cells are phenotypically and functionally distinct from the usual Th2 cells and produce a large amount of IL-5. Since these cells survive and continue to function at the inflamed sites, they are important in chronic inflammation. Next, Prof. Kubo explains follicular helper (TFH) cells.4 TFH cells are a subset of CD4þ helper T cells and play a critical role in antibody maturation in germinal center. IgE and IgG1 antibody responses, important events in type 2 inflammation, are mainly controlled by IL-4esecreting TFH cells, not by Th2 cells. Then Prof. Karasuyama's group discusses the roles of basophils in allergic inflammation.5 Basophils have long been neglected in immunological studies as only minor relatives of mast cells. However, it has recently turned out that basophils play non-redundant roles in both IgE-dependent and -independent allergic inflammation. It is