Issues

Irene Salinas’s lab uses multiple animal models to study nasal immunity and neuroimmune interactions in the olfactory–central nervous system axis in response to microorganisms. We spoke with Irene about her lab work and her diversity, equity, and inclusion (DEI) work.

In this issue of JEM, Davidson et al. and Takeda et al. independently report on a dominant negative form of OTULIN deficiency in three unrelated patients.

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.

Matthias Eberl and Sheena Cruickshank discuss the need for public involvement and engagement in biomedical research and ongoing major systemic challenges.

Treg cells are classically known for their critical immunosuppressive functions. More recent work demonstrates that Treg cells produce mediators that facilitate tissue repair. This review examines the interactions between Treg cells and tissue-specific non-immune cells that mediate repair and regeneration following sterile or infectious damage.

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.

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.

This study describes an OTULIN-related autoinflammatory syndrome (ORAS) patient with two rare heterozygous variants of OTULIN (p.P152L and p.R306Q); the latter is a de novo variant that acts in a dominant-negative manner to cause ORAS.

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.

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).

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.

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.

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.