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Cytokine release syndrome (CRS) is a significant side effect associated with chimeric antigen receptor (CAR)-T cell therapy for cancer. CAR-T cells engineered to secrete cytokine modulators can reduce CRS-related toxicity while simultaneously improving in vivo antitumor efficacy.

Schmitt, Duval, et al. show that TL1A is an epithelial cytokine that cooperates with IL-33 in the initiation of allergic airway inflammation. Similar to IL-33, TL1A functions as an alarmin important for early induction of IL-9high ILC2s after allergen exposure.

CD4+ T cells exhibit pleiotropic roles in autoimmunity and cancer. Lalle et al. demonstrate that their function is selectively controlled by different NF-κB subunits depending on the disease context. This work unravels critical regulators of T cell function and paves the way toward NF-κB subunit–targeted immunotherapies.

SARS-CoV-2 cell tropism and infection cycle are defined at the cellular resolution by infection of healthy human lung tissue and single-cell profiling. Interstitial macrophages are a dominant target of viral takeover, inflammation, and destruction in COVID-19 initiation, and use DC-SIGN/CD209, but not ACE2, for entry.

Horesh et al. use forward and reverse genetics to identify four novel gain-of-function JAK1 mutations in 59 patients. These individuals present with autoimmunity, atopy, colitis, and/or dermatitis, suggestive of a novel syndrome termed JAK1-associated atopy colitis and/or dermatitis (JAACD).

Technical Advances and Resources

The poor prognosis of M3 uveal melanomas generates a local adaptive immune response, which does not recirculate, while the better prognosis of SF3B1-mutated uveal melanomas induces a systemic immune response in the absence of a detectable local response.

Insights

In this issue, Schmitt et al. identify TNF-like protein 1A (TL1A) as an epithelial alarmin constitutively expressed by a subset of lung epithelial cells, which is released in response to airborne microbial challenge and synergizes with IL-33 to drive allergic disease.

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