PIR-B Regulates CD4+ IL17a+ T-Cell Survival and Restricts T-Cell–Dependent Intestinal Inflammatory Responses

Abstract

The inhibitory receptor paired immunoglobulin-like receptor B regulates CD4 þ T-helper 17 cell-dependent chronic intestinal inflammatory responses by tempering mammalian target of rapamycin complex Q8 1 signaling and enhancing CD4 þ interleukin 17a þ T-cell survival and regulates the outgrowth and maintenance of tissue resident memory CD4 þ interleukin 17a þ T cells.BACKGROUND & AIMS: CD4 þ T cells are regulated by activating and inhibitory cues, and dysregulation of these proper regulatory inputs predisposes these cells Q9 to aberrant inflammation and exacerbation of disease. We investigated the role of the inhibitory receptor paired immunoglobulin-like receptor B (PIR-B) in the regulation of the CD4 þ T-cell inflammatory response and exacerbation of the colitic phenotype. METHODS:We used Il10 -/spontaneous and CD4 þ CD45RB hi Tcell transfer models of colitis with PIR-B-deficient (Pirb -/-) mice. Flow cytometry, Western blot, and RNA sequencing analysis was performed on wild-type and Pirb -/-CD4 þ T cells. In silico analyses were performed on RNA sequencing data set of ileal biopsy samples from pediatric CD and non-inflammatory bowel disease patients and sorted human memory CD4 þ T cells. RESULTS:We identified PIR-B expression on memory CD4 þ interleukin (IL)17a þ cells. We show that PIR-B regulates CD4 þ T-helper 17 cell (Th17)-dependent chronic intestinal inflammatory responses and the development of colitis. Mechanistically, we show that the PIR-B-SHP Q10 -1/2 axis tempers mammalian Q11 target of rapamycin complex 1 signaling and

Research progress on intestinal tissue‐resident memory T cells in inflammatory bowel disease

“…Its loss of function inhibited the differentiation and growth of CD4 + IL17A + T RM cells, thus protecting against the development of CD4 + T cell-dependent colitis in a T cell transfer mouse model. 110 These studies showed that the number of T RM cells in the intestines of patients with IBD increased, and that they had a stronger pro-inflammatory capacity. This may be due to the regulation of transcription factors, such as Eomes.…”

“…Similarly, the paired immunoglobulin‐like receptor B intrinsically regulates CD4 + IL17A + T cell survival. Its loss of function inhibited the differentiation and growth of CD4 + IL17A + T RM cells, thus protecting against the development of CD4 + T cell‐dependent colitis in a T cell transfer mouse model 110 …”

Dual role of ANGPTL8 in promoting tumor cell proliferation and immune escape during hepatocarcinogenesis

“…Our previous study identified a direct interaction between ANGPTL8 and the PIRB receptor [ 16 ], which corresponds to LILRB2 in humans [ 40 ]. LILRB2/PIRB is an inhibitor of inflammation and autoimmunity [ 41 ], and LILRB2 blockade with antagonizing antibodies increases tumor cell death and the killing activity of cytotoxic T lymphocytes [ 20 ]. We found that ANGPTL8 colocalized with LILRB2/PIRB on the cell membrane, and a chimeric receptor assay confirmed a direct interaction between them.…”

The IRE1α/XBP1 pathway sustains cytokine responses of group 3 innate lymphoid cells in inflammatory bowel disease

“…The mice were weighed every 5 days after transfer. The clinical score was graded on a scale of 0 to 5 and was based on decreased activity, hunched posture, ruffled fur, rate of breathing, shrunken eyes, shivering, rectal bleeding, and diarrhea as previously described ( 65 , 66 ). The mice were euthanized on day 45 after transfer, and the colons were collected for measurement of length and histological analysis.…”