Regulatory roles of dermal type 2 innate lymphoid cells

摘要: Type 2 immune immunity evolved a unique system to protect against noxious xenobiotics at the epithelial barrier.1 Recently, cell-derived cytokines IL-25, IL-33 and TSLP have been shown be critical in producing Th2 cytokines, including IL-4, IL-5, IL-9 IL-13, by type innate lymphoid cells (ILC2s) as well cells. Even though numerous studies demonstrated that ILC2s are able initiate variety of reactions associated with responses independently cells, little is known about whether they control activity other In paper published Nature Immunology, Roediger et al.2 two different mechanisms could crucial for maintaining skin homeostasis under steady state conditions mediating inflammation. Innate differentiated from Id2-expressing common but specification subsets determined transcription factors.3 Two transcript factors GATA-3 RORα required ILC2 differentiation.3 heterogeneous terms their phenotypes tissue distribution. However, effector functions commonly mediated through soluble factors. Given intrinsic properties location organs mucosal sites, considered first line defense allergens parasitic infections. plays an essential role repair experience damage resulting overly exuberant responses, found participate lung after infection influenza virus.4 addition, maintain visceral adipose eosinophils M2 macrophages regulate metabolic homeostasis.5 identified dermal express CD103 (αEβ7 integrin expressed skin-resident T cells) constitutively IL-13. Using reporter mice, convincingly patrol interact mast vitro experiments, IL-13 has inhibit ability primed product IL-6 TNF upon exposure antigen. On hand, another independent research group indispensible atopic dermatitis (AD)-like disease induced vitamin D3 analog MC903.6 This chemical potent inducer (but not IL-25 IL-33) production keratinocytes. Which cytokine produced among barriers seems types allergens, parasites injury inducers, responding parenchymal stromal The MC903 result AD-like inducing keratinocytes.7 One important finding treatment complexes IL-2 anti-IL-2 monoclonal antibody (potently stimulate receptor) Rag1−/− mice elicits characteristics eosinphil infiltrates activated expansion IL-5-producing ILC2s. It remains allergen-primed can during allergic cell-replete mice. Although potentiate proliferation activation IL-25- and/or IL-33-rich milieu, may directly act on such these acute phase no longer present inflamed sites. There compelling evidence papain-induced inflammation, adaptive transit subsequently results IL-5 autocrine fashion.8 observation suggest once initiated, it recruit all available, ILC2s, reinforce responses.9 Dermal tropism due expression cell surface abundance skin. If this turns out case, continuously circulate body immunosurveillance suggested extensive interactions provision signals might mechanism which capable suppressing (Figure 1a). But what meaning immunosupression naive state? sensitize ligand–receptor secretion sensitization raise threshold activation, function safety brake prevent unnecessary inflammation.10 also possible promote immunomodulatory molecules IL-10 TGF-β report showing inhibiting inflammation.11 Therefore, overall consequences regulatory networking seem uncontrollable excessive inflammation. Figure 1 Roles inflammation. (a) unknown pair suppress IL-13-primed ... The observations indicate having mediate inflammation allergens. As mentioned previously, major stimulator progression disease, presumably keratinocytes do produce response 1b). alone sufficient induce critically affect T-cell instructing differentiation MHC class II8 numbers increased draining lymph node inflammation,6 CD4+ antigen presentation priming or response. Indeed, regulation reported ILC3s:12 lacking appropriate costimualtory ligands generation tolerogenic cells.12 will interesting investigate similar negative 1c). Recently, clear lineage marker-negative derived progenitors divided into three groups based Th1, Th17 cytokines. Allergens mount both responses. context, antigens ILC1 ILC3 preferentially Th1 respectively. merit if ILCs successful, initiation Th Then corresponding Foxp3+CD4+ exist? Or there cross-regulation one ILC subset subset? These issues exciting area solved near future.