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The signals driving the adaptation of type 2 dendritic cells (DC2s) to diverse peripheral environments remain mostly undefined. We show that differentiation of CD11blo migratory DC2s-a DC2 population unique to the dermis-required IL-13 signaling dependent on the transcription factors STAT6 and KLF4, whereas DC2s in lung and small intestine were STAT6-independent. Similarly, human DC2s in skin expressed an IL-4 and IL-13 gene signature that was not found in blood, spleen and lung DCs. In mice, IL-13 was secreted homeostatically by dermal innate lymphoid cells and was independent of microbiota, TSLP or IL-33. In the absence of IL-13 signaling, dermal DC2s were stable in number but remained CD11bhi and showed defective activation in response to allergens, with diminished ability to support the development of IL-4+GATA3+ helper T cells (TH), whereas antifungal IL-17+RORγt+ TH cells were increased. Therefore, homeostatic IL-13 fosters a noninflammatory skin environment that supports allergic sensitization.

New Zealand has avoided the major health impacts of the SARS-CoV-2 pandemic due to a strict country-wide lockdown, the end-goal of which was elimination rather than mitigation and suppression. The New Zealand government’s use of scientific expertise, spanning public health, infectious diseases, genomics, modeling and immunology, has been one of the keys to the success of its SARS-CoV-2 elimination and control strategy.

Defining the immune mechanisms underlying protective immunity to helminth infection remains an important challenge. Here we report that lung CD4(+) T cells and Group 2 innate lymphoid cells (ILC2s) work in concert to block Nippostrongylus brasiliensis (Nb) development in the parenchyma within 48 h in mice. Immune-damaged larvae have a striking morphological defect that is dependent on the expansion of IL-13-producing ILC2 and CD4(+) T cells, and the activation of M2 macrophages. This T-cell requirement can be bypassed by administration of IL-2 or IL-33, resulting in expansion of IL-13-producing ILC2s and larval killing. Depletion of ILC2s inhibits larval killing in IL-2-treated mice. Our results broaden understanding of ILC2's role in immunity to helminths by demonstrating that they not only act as alarmin sensors, but can also be sustained by CD4(+) T cells, ensuring both the prompt activation and the maintenance of IL-13-dependent M2 macrophage immunity in the lung.

A cohort of immunodeficient children lead near-normal lives after bone marrow transplantation, despite a profound deficiency of innate lymphoid cells (ILCs).

Asthma is an atopic disorder characterised by the activation and recruitment of eosinophils to the lung resulting in chronic swelling and inflammation of the airways. Allergic disorders such as atopic asthma and dermatitis have been increasingly prevalent in developed countries, and the inverse correlation between exposure to major diseases such as tuberculosis and atopy prevalence has been reported. Intranasal administration of Mycobacterium bovis-Bacillus Calmette-Guerin (BCG) has been demonstrated to suppress airway eosinophilia in a model of atopic asthma. This immunomodulation is attributed to the ability of interferon (IFN)-gamma produced by BCG-specific T(H)1 lymphocytes to inhibit the development of lung T(H)2 responses such as airway eosinophilia. The mechanism of IFNgamma-induced inhibition is yet to be defined, but could involve activation of macrophages, direct suppression of developing T(H)2 lymphocytes, or altered dendritic cell activation and antigen presentation. Mycobacteria such as BCG and certain mycobacterial fractions are strong inducers of a T(H)1 immune response. The effectiveness of BCG in inhibiting atopic airway eosinophilia suggests its potential as a useful therapeutic agent in the treatment of atopic asthma.