Homeostatic IL-13 in healthy skin directs dendritic cell differentiation to promote TH2 and inhibit TH17 cell polarization

ILC2‐derived IL‐13 promotes skin cDC2 diversity

“…While cDC1s depend on the transcription factor IRF8 for their development and are specialized into cross-presenting cell-associated antigens to CD8 + T cells, cDC2s are IRF8 independent and more preferentially are required for CD4 + T-cell priming and Th responses. 2,3 Mayer et al 1 examined the cDC populations in the mouse skin and found that cDC2s can be separated into CD11b hi and CD11b lo fractions, a finding compatible with previous studies. 4,5 CD11b lo cDC2s were absent from other tissues examined, including the small intestine and lung, suggestive of the existence of a particular milieu imprinting cDC2 diversity in the skin.…”

“…Although this observation corroborated a previous finding, 4 it is difficult to reconcile with the key role proposed for dermal cDC2s expressing CD301b/ MGL2 in mediating Th2 immunity, 7 as a later study showed that CD301b expression is restricted to the same skin migratory CD11b hi cDC2s 4 that Mayer et al demonstrated are IL-13 independent. 1 The nature of this discrepancy warrants further investigation.…”

“…To search for the cellular source of IL-13 in the skin, Mayer et al 1 used an IL-13-DsRed reporter strain and found that approximately half of the constitutive IL-13 expressing cells were type 2 innate lymphoid cells (ILC2s). This agrees with a previous report identifying ILCs as the main source of IL-13 in unchallenged murine skin.…”

“…Mayer et al 1 then investigated whether this signaling axis also plays a role in the immune response in the skin. To exclude roles for this pathway in non-cDCs, such as T cells, these studies were conducted in chimeric mice where all cDC2s where either wild type or STAT6 deficient and the wild-type T cells could be identified based on congenic markers.…”

“…Collectively, the study by Mayer et al 1 adds to a growing body of evidence of tissue cDC2 diversity, identifying a unique subset of cDC2s in the skin that impacts on the capacity of the immune system to promote Th2 immunity. Although the IL-13-STAT6 homeostatic axis may be restricted to the skin, cDC2 diversity is apparent in other tissues, as, for example, has been shown in the lung after allergen challenge.…”