Johnson, Ogishi, and Domingo-Vila et al. describe two siblings with inherited PD-L1 deficiency. Human PD-L1 deficiency underlies early-onset T1D, like PD-1 deficiency, but does not lead to fatal autoimmunity with extensive leukocytic dysregulation, unlike PD-1 deficiency.

This study identifies a novel dominant negative heterozygous mutation in OTULIN (p.Cys129S). C129S OTULIN promotes accumulation of linear ubiquitin chains on diverse substrates including LUBAC, causing enhanced cell death and inflammatory signaling, and thereby this heterozygous mutation drives autoinflammatory disease.

Midnolin is an essential gene with previously unknown effects in vivo. This paper shows that midnolin stimulates proteasome activity necessary for lymphopoiesis and B cell cancer growth in mice.

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-9^high ILC2s after allergen exposure.

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.

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.