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Innate lymphoid cells (ILCs) are important for tissue immune homeostasis, and are thoroughly characterized in mice and humans. Here, we have performed in‐depth characterization of rat ILCs. Rat ILCs were identified based on differential expression of transcription factors and lack of lineage markers. ILC3s represented the major ILC population of the small intestine, while ILC2s were infrequent but most prominent in liver and adipose tissue. Two major subsets of group 1 ILCs were defined. Lineage–T‐bet+Eomes+ cells were identified as conventional NK cells, while lineage–T‐bet+Eomes– cells were identified as the probable rat counterpart of ILC1s based on their selective expression of the ILC marker CD200R. Rat ILC1s were particularly abundant in liver and intestinal tissues, and were functionally similar to NK cells. Single‐cell transcriptomics of spleen and liver cells confirmed the main division of NK cells and ILC1‐like cells, and demonstrated Granzyme A as an additional ILC1 marker. We further report differential distributions of NK cells and ILCs along the small and large intestines, and the association of certain bacterial taxa to frequencies of ILCs. In conclusion, we provide a framework for future studies of ILCs in diverse rat experimental models, and novel data on the potential interplay between commensals and intestinal ILCs. [ABSTRACT FROM AUTHOR]

Clonally related B cells infiltrate the brain, meninges, and cerebrospinal fluid of MS patients, but the mechanisms driving the B‐cell response and shaping the immunoglobulin repertoires remain unclear. Here, we used single‐cell full‐length RNA‐seq and BCR reconstruction to simultaneously assess the phenotypes, isotypes, constant region polymorphisms, and the paired heavy‐ and light‐chain repertoires in intrathecal B cells. We detected extensive clonal connections between the memory B cell and antibody‐secreting cell (ASC) compartments and observed clonally related cells of different isotypes including IgM/IgG1, IgG1/IgA1, IgG1/IgG2, and IgM/IgA1. There was a strong dominance of the G1m1 allotype constant region polymorphisms in ASCs, but not in memory B cells. Tightly linked to the G1m1 allotype, we found a preferential pairing of the immunoglobulin heavy‐chain variable (IGHV)4 gene family with the κ variable (IGKV)1 gene family. The IGHV4‐39 gene was most used and showed the highest frequency of pairing with IGKV1‐5 and IGKV1(D)‐33. These results link IgG constant region polymorphisms to stereotyped B‐cell responses in MS and indicate that the intrathecal B‐cell response in these patients could be directed against structurally similar epitopes. [ABSTRACT FROM AUTHOR]

Human C‐type lectin‐like CD161 is a type‐II transmembrane protein expressed on the surface of various lymphocytes across innate and adaptive immune systems. CD161+ T cells displayed enhanced ability to produce cytokines and were shown to be enriched in the gut. Independently of function, CD161 was used as marker of innate‐like T cells and marker of IL‐17‐producing cells. The function of CD161 is still not fully understood. In T cells, CD161 was proposed to act as co‐signalling receptor that influence T‐cell receptor‐dependent responses. However, conflicting studies were published demonstrating lack of agreement over the role of CD161 during T‐cell activation. In this review, we outline phenotypical and functional consequences of CD161 expression in T cells. We provide critical discussion over the most pressing issues including in depth evaluation of the literature concerning CD161 putative co‐signalling properties. [ABSTRACT FROM AUTHOR]

C‐type lectin‐like CD161, a class II transmembrane protein, is a surface receptor expressed by NK cells and T cells. In coeliac disease, CD161 was expressed more frequently on gluten‐reactive CD4 + T cells compared to other memory CD4 + T cells isolated from the same tissue compartment. CD161 is a putative co‐signalling molecule that was proposed to act as co‐stimulatory receptor in the context of signalling through TCR, but contradicting results were published. In order to understand the role of CD161 in gluten‐reactive CD4 + T cells, we combined T cell stimulation assays or T cell proliferation assays with ligation of CD161 and intracellular cytokine staining. We found that CD161 ligation provided neither co‐stimulatory nor co‐inhibitory signals to modulate proliferation and IFN‐γ or IL‐21 production by gluten‐reactive CD4 + T cell clones. Thus, we suggest that CD161 does not function as a co‐signalling receptor in the context of gluten‐reactive CD4 + T cells. [ABSTRACT FROM AUTHOR]

Keywords: celiac; gluten; HLA-DQ2.5; mouse; TCR EN celiac gluten HLA-DQ2.5 mouse TCR 1002 1005 4 04/19/21 20210401 NES 210401 We created a TCR transgenic mouse with CD4 SP + sp T cells recognizing the immunodominant DQ2.5-glia- 2 gluten epitope. We have recently created transgenic (tg) mice expressing celiac patient-derived T-cell receptors (TCRs) recognizing the DQ2.5-glia- 2 gluten epitope [3] and here report the generation of a TCR tg mouse specific for the DQ2.5-glia- 2 epitope. Characterization of T-cell receptor transgenic mice recognizing immunodominant HLA-DQ2.5-restricted gluten epitopes. [Extracted from the article]