Biology subjects

Johansson, M. H.

Publications and source records attributed to Johansson, M. H..

3 recordsLinked to original sources

bioRxiv2026

Intratumoral expression of JAML on NK cells is controlled by tumor microenvironment and MHC class I interaction

Junctional adhesion molecule-like (JAML) is an adhesion molecule known to promote T cell activation and T cell-mediated tumor rejection. In the current study, we show that JAML expression is enriched on mouse intratumoral NK cells compared with splenic NK cells. JAML+ NK cells were associated with tissue residency and co-expressed the immune checkpoints PD-1 and LAG3. JAML expression could be induced on splenic NK cells by IL-2 and further enhanced by IL-21. JAML levels were inversely correlated with inhibitory signaling, as NK cells expressing self-recognizing Ly49 receptors had reduced JAML expression, suggesting regulation of JAML expression by MHC class I molecules. Interaction with the JAML ligand CXADR also reduced JAML surface expression, indicating that tumor-mediated membrane stripping may represent a mechanism of immunoediting. Although JAML RNA transcripts were detectable in human NK cells, JAML protein was found only intracellularly. Together, these findings identify the JAML-CXADR interaction as a potential regulatory pathway in NK cell-mediated killing of tumors.

immunology↗

bioRxiv2026

Implantation failure linked to altered uterine NK cells in PCOS-like mice

Uterine NK (uNK) cells are essential for reproductive function, yet little is known how they are affected in polycystic ovary syndrome (PCOS), despite the strong association between PCOS and reproductive complications. We demonstrate that implantation failure coincides with distinct phenotypic alterations of uNK cells in a PCOS-like mouse model. Hyperandrogenism caused an increased influx of conventional NK (cNK) cells into the uterus, which contributed to an augmented uNK cell population, while tissue-resident NK (trNK) cells remained unchanged. Notably, CD69+ trNK cells were reduced and seemingly compensated by an upregulated expression of CD69 on cNK cells in the uterus. The maturation of uNK cells was disrupted and plausibly linked to an inability of cNK cells to convert into trNK cells. The inhibited maturation was associated with a reduced expression of the inhibitory receptor NKG2A, demonstrating an impaired education of uNK cells. This disruption of uNK cells could contribute to endometrial dysfunction and may be an underlying factor to reproductive comorbidities such as implantation failure, miscarriage and pre-eclampsia in PCOS.

immunology↗

bioRxiv2024

Androgens modulate the immune profile in a mouse model of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is associated with a low-grade inflammation, but it is unknown how hyperandrogenism, the hallmark of PCOS, affects the immune system. Using a well-established PCOS-like mouse model, we demonstrate that androgen exposure affects immune cell populations in reproductive, metabolic, and immunological tissues differently in a site-specific manner. Co-treatment with flutamide, an androgen receptor antagonist, prevents most of these alterations, demonstrating that these effects are mediated through androgen receptor activation. Dihydrotestosterone (DHT)-exposed mice display a drastically reduced eosinophil population in uterus compared to controls, coupled with lower levels of eotaxin (CCL11), suggesting a reduced recruitment from blood. Decreased frequencies of eosinophils were also seen in visceral adipose tissue (VAT). A higher expression level of CD69, a marker of activation or tissue residency, was consistently found on natural killer (NK) cells in all analyzed tissues. However, a higher frequency of NK cells and elevated levels of IFN-{gamma} and TNF- were only seen in uteri of androgen-exposed mice, while NK cell frequencies were unaffected in all other analyzed compartments. Distinct alterations of macrophages in ovaries, uterus and VAT were also found in DHT-exposed mice and could potentially be linked to PCOS-like traits of the model. Indeed, androgen-exposed mice were insulin resistant and displayed an aberrant immune profile in VAT, albeit unaltered fat mass. Collectively, we demonstrate that hyperandrogenism causes tissue-specific alterations of immune cells in reproductive organs and VAT, which could have considerable implications on tissue function and contribute to the reduced fertility and metabolic comorbidities associated with PCOS.

immunology↗